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  • 1. Andersson, N.
    et al.
    Strandberg, L.
    Nilsson, S.
    Adamovic, S.
    Karlsson, M. K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mellström, D.
    Lane, N. E.
    Zmuda, J. M.
    Nielsen, C.
    Orwoll, E.
    Lorentzon, M.
    Ohlsson, C.
    Jansson, J-O.
    A variant near the interleukin-6 gene is associated with fat mass in Caucasian men2010In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 34, no 6, p. 1011-1019Article in journal (Refereed)
    Abstract [en]

    Context:Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity.Objective:To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity.Design and Study Subjects:The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies.Main Outcome:The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry.Results:Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat.Conclusions:The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.

  • 2. Andersson, N
    et al.
    Strandberg, L
    Nilsson, S
    Ljunggren, O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, K
    Mellström, D
    Lorentzon, M
    Ohlsson, C
    Jansson, J.-O.
    Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men2009In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 33, no 5, p. 525-533Article in journal (Refereed)
    Abstract [en]

    Context: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. Objective: To systematically investigate our hypotheses that single- nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. Subjects: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n = 1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n = 3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. Main Outcome Measure: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). Results: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 30 untranslated region C4T (rs4252041, minor allele frequency 4%) SNP was associated with the primary outcome total fat mass (P = 0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN_2018 T4C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P = 0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P < 0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. Conclusions: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have no previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men. International Journal of Obesity (2009) 33, 525-533; doi: 10.1038/ijo.2009.47; published online 17 March 2009

  • 3.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Burgos, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, M J
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2, p. 230-236Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: 

    Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes.

    DESIGN: 

    Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task.

    SUBJECTS: 

    A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m−2) or obese (30 kg m−2).

    RESULTS: 

    People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight.

    CONCLUSION: 

    These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

  • 4. Carlsson, A. C.
    et al.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Engstrom, G.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Melander, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Leander, K.
    Gigante, B.
    Hellenius, M-L
    de Faire, U.
    Novel and established anthropometric measures and the prediction of incident cardiovascular disease: a cohort study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 12, p. 1579-1585Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmo Diet and Cancer study-cardiovascular cohort). METHODS: This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated. RESULTS: All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n = 5180), WHHR was the only measure that improved Cox regression models in men (P = 0.01). CONCLUSION: WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.

  • 5. Cnattingius, S.
    et al.
    Villamor, E.
    Lagerros, Y. T.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Granath, F.
    High birth weight and obesity: a vicious circle across generations2012In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 10, p. 1320-1324Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Rates of high birth weight infants, overweight and obese children and adults are increasing. The associations between birth weight and adult weight may have consequences for the obesity epidemic across generations. We examined the association between mothers' birth weight for gestational age and adult body mass index (BMI) and these factors' joint effect on risk of having a large-for-gestational-age (LGA) offspring (>+2 s.d. above the mean). DESIGN: A cohort of 162 676 mothers and their first-born offspring with birth information recorded on mothers and offspring in the nation-wide Swedish Medical Birth Register 1973-2006. RESULTS: Compared with mothers with appropriate birth weight for gestational age (AGA; -1 to +1 s.d.), mothers born LGA had increased risks of overweight (BMI 25.0-29.9; odds ratio (OR), 1.50; 95% CI 1.39-1.61), obesity class I (BMI 30.0-34.9; OR 1.77; 95% CI 1.59-1.98), obesity class II (BMI 35.0-39.9; OR 2.77; 95% CI 2.37-3.24) and obesity class III (BMI >= 40.0; OR 2.04; 95% CI 1.49-2.80). In each stratum of mother's birth weight for gestational age, risk of having an LGA offspring increased with mother's BMI. The risk of an LGA offspring was highest among women with a high (>= 30) BMI who also had a high birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI (<= 24.9). However, the strongest increase in risk by BMI was seen among mothers born SGA: the OR of having an LGA offspring was 13 times as high among SGA mothers with BMI >= 35.0 compared with the OR among SGA mothers with normal BMI (ORs = 4.61 and 0.35, respectively). CONCLUSIONS: Prenatal conditions are important for the obesity epidemic. Prevention of LGA births may contribute to curtail the intergenerational vicious cycle of obesity.

  • 6. Dahl, A. K.
    et al.
    Reynolds, C. A.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Magnusson, P. K. E.
    Pedersen, N. L.
    Multifactorial analysis of changes in body mass index across the adult life course: a study with 65 years of follow-up2014In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 38, no 8, p. 1133-1141Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although the negative consequences on health of being obese are well known, most adults gain weight across the lifespan. The general increase in body mass index (BMI) is mainly considered to originate from behavioral and environmental changes; however, few studies have evaluated the influence of these factors on change in BMI in the presence of genetic risk. We aimed to study the influence of multifactorial causes of change in BMI, over 65 years. METHODS AND FINDINGS: Totally, 6130 participants from TwinGene, who had up to five assessments, and 536 from the Swedish Adoption/Twin Study of Aging, who had up to 12 assessments, ranging over 65 years were included. The influence of lifestyle factors, birth cohort, cardiometabolic diseases and an individual obesity genetic risk score (OGRS) based on 32 single nucleotide polymorphisms on change in BMI was evaluated with a growth model. For both sexes, BMI increased from early adulthood to age of 65 years, after which the increase leveled off; BMI declined after age of 80 years. A higher OGRS, birth after 1925 and cardiometabolic diseases were associated with higher average BMI and a steeper increase in BMI prior to 65 years of age. Among men, few factors were identified that influence BMI trajectories in late life, whereas for women type 2 diabetes mellitus and dementia were associated with a steeper decrease in BMI after the age of 65 years. CONCLUSIONS: There are two turning points in BMI in late adulthood, one at the age of 65 years and one at the age 80 years. Factors associated with an increase in BMI in midlife were not associated with an increase in BMI after the age of 65 years. These findings indicate that the causes and consequences of change in BMI differ across the lifespan. Current health recommendations need to be adjusted accordingly.

  • 7. den Hoed, M
    et al.
    Luan, J
    Langenberg, C
    Cooper, C
    Sayer, A A
    Jameson, K
    Kumari, M
    Kivimaki, M
    Hingorani, A D
    Grøntved, A
    Khaw, K-T
    Ekelund, U
    Wareham, N J
    Loos, R J F
    Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples.2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.

    OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based samples.

    DESIGN: Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.

    RESULTS: We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (β=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).

    CONCLUSION: Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.

  • 8. den Hoed, M
    et al.
    Smeets, A J P G
    Veldhorst, M A B
    Nieuwenhuizen, A G
    Bouwman, F G
    Heidema, A G
    Mariman, E C M
    Westerterp-Plantenga, M S
    Westerterp, K R
    SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis.2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The postprandial responses in (an)orexigenic hormones and feelings of hunger are characterized by large inter-individual differences. Food intake regulation was shown earlier to be partly under genetic control.

    OBJECTIVE: This study aimed to determine whether the postprandial responses in (an)orexigenic hormones and parameters of food intake regulation are associated with single nucleotide polymorphisms (SNPs) in genes encoding for satiety hormones and their receptors.

    DESIGN: Peptide YY (PYY), glucagon-like peptide 1 and ghrelin levels, as well as feelings of hunger and satiety, were determined pre- and postprandially in 62 women and 41 men (age 31+/-14 years; body mass index 25.0+/-3.1 kg/m(2)). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire. SNPs were determined in the GHRL, GHSR, LEP, LEPR, PYY, NPY, NPY2R and CART genes.

    RESULTS: The postprandial response in plasma ghrelin levels was associated with SNPs in PYY (215G>C, P<0.01) and LEPR (326A>G and 688A>G, P<0.01), and in plasma PYY levels with SNPs in GHRL (-501A>C, P<0.05) and GHSR (477G>A, P<0.05). The postprandial response in feelings of hunger was characterized by an SNP-SNP interaction involving SNPs in LEPR and NPY2R (668A>G and 585T>C, P<0.05). Dietary restraint and disinhibition were associated with an SNP in GHSR (477G>A, P<0.05), and perceived hunger with SNPs in GHSR and NPY (477G>A and 204T>C, P<0.05).

    CONCLUSIONS: Part of the inter-individual variability in postprandial responses in (an)orexigenic hormones can be explained by genetic variation. These postprandial responses represent either long-term physiological adaptations to facilitate homeostasis or reinforce direct genetic effects.

  • 9. den Hoed, M
    et al.
    Westerterp, K R
    Body composition is associated with physical activity in daily life as measured using a triaxial accelerometer in both men and women.2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Activity-related energy expenditure is the most variable component of total energy expenditure and thus an important determinant of energy balance.

    OBJECTIVE: To determine whether body composition is related to physical activity in both men and women.

    DESIGN: A total of 134 healthy participants were recruited (80 women, 54 men; aged 21+/-2 years; body mass index, 22.0+/-2.4). Physical activity was measured for a period of 2 weeks using a triaxial accelerometer for movement registration (Tracmor). Percentage body fat (%BF) was determined by underwater weighing and deuterium dilution according to Siri's three-compartment model.

    RESULTS: The participant characteristics-body mass, height and gender together explained a substantial part of the variation in %BF (R(2)=0.75, SEE=4.0%). Adding physical activity to the model increased the explained variation in %BF with 4% (R(2)=0.79, SEE=3.7%, P<0.001). Taking seasonality into account by adding the number of daylight hours as an independent variable further increased the explained variation with 1% (R(2)=0.80, SEE=3.7%, P<0.05). In analogy, the association was evaluated for both genders separately. In women, %BF and physical activity were significantly associated (P<0.001). In men, %BF was only associated with physical activity when seasonality was taken into account as well (P<0.05). This probably resulted from men participating more in season bound sports, because an association was found without adjusting for seasonality when only men with a consistent year-round participation in sports were considered.

    CONCLUSION: Evidence was found for an association between body composition and physical activity in both genders. A consistent year-round degree of physical activity appears to be a prerequisite to reveal the association. Moreover, Tracmor-assessed physical activity improves the estimate of %BF when a participant's characteristics are taken into account.

  • 10. Eliasson, B
    et al.
    Gudbjörnsdottir, S
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Liang, Y
    Vercruysse, F
    Smith, U
    Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double-blind placebo-controlled trial2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, no 7, p. 1140-1147Article in journal (Refereed)
    Abstract [en]

    Objective:

    To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months.

    Design and subjects:

    Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebo-controlled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase).

    Measurements:

    Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion.

    Results:

    The mean age was 58.67.1 years, body weight 98.116.1 kg, BMI 33.04.5 kg/m2, and glycosylated hemoglobin (HbA1c) 7.30.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.10.9%), fasting plasma glucose, body weight (-6.63.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate.

    Conclusions:

    Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.

  • 11.
    Engström, Björn E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Karlsson, F. Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, no 3, p. 476-480Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined. DESIGN: Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal (770 kcal). SUBJECTS: Twenty men and 20 women were included: 10 middle-aged morbidly obese (body mass index (BMI) 43.9+/-3.3 kg/m(2)), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.7+/-5.8 kg/m(2)), 10 middle-aged non-obese (BMI 23.5+/-2.2 kg/m(2)) and 10 young non-obese (BMI 22.7+/-1.8 kg/m(2)). MEASUREMENTS: Ghrelin, glucose and insulin levels were analysed pre- and postprandially. RESULTS: In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both age-matched and young non-obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression. CONCLUSION: The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.

  • 12. Gao, Weiguo
    et al.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Qiao, Q
    Tuomilehto, J
    Balkau, B
    Ruotolo, G
    Calor, G
    Garancini, MP
    Alberti, K
    Stelhouwer, C
    Does the constellation of risk factors with and without abdominal adiposity associate with different cardiovascular mortality risk?2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, p. 757-762Article in journal (Refereed)
  • 13.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, Linda Solstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, A. L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 11, p. 1687-1692Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied.

    OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI).

    METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m(-)(2)) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m(-)(2)), both before and 30 min after consumption of a standardized meal (~260 kcal).

    RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups.

    CONCLUSION: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.International Journal of Obesity advance online publication, 28 June 2016; doi:10.1038/ijo.2016.105.

  • 14.
    Holdstock, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eden Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Karlsson, Anders
    CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects2005In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 29, no 10, p. 1275-1280Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk ofcardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent theinsulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypasssurgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies onthe regulation of inflammatory markers.DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects.

    SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery.

    MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well asmarkers of glucose and lipid metabolism.

    RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRPcorrelated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, whencorrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the changein body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4(insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended toparallel the changes in CRP, but were less informative.

    CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers andimproves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistantpatients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather thanenergy supply.

  • 15.
    Holdstock, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Postprandial changes in gut regulatory peptides in gastric bypass patients2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, p. 1640-6Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding. DESIGN: The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal. SUBJECTS: Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41+/-7 years; mean BMI 44+/-3 kg/m(2)), 10 operated with RYGBP (age 45+/-5 years; BMI 35+/-6 kg/m(2)), 10 aged-matched lean (age 44+/-5 years; BMI 24+/-3 kg/m(2)) and 10 young lean subjects (age 26+/-2 years; BMI 23+/-2 kg/m(2)). MEASUREMENTS: Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained. RESULTS: PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect. CONCLUSION: RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre- and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.

  • 16. Hong, N-S
    et al.
    Kim, K-S
    Lee, I-K
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jacobs, D R
    Lee, D-H
    The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox2011In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 9, p. 1170-1175Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Numerous studies have documented an obesity paradox in which the overweight and obese elderly have a better prognosis than those with ideal body weight. Good prognosis among the overweight or obese elderly may reflect the relative safety of storing the harmful lipophilic chemicals, known as persistent organic pollutants (POPs), in adipose tissue rather than in other critical organs. Therefore, we hypothesized lower mortality among the obese elderly with a higher body burden of POPs, but this pattern may not exist among the obese elderly with a lower body burden of POPs.

    PARTICIPANTS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2004 study with a mean 4.2-year follow-up, we tested whether the association between fat mass and total mortality in 635 (652 for organochlorine pesticides) elderly participants aged >= 70 years differed depending on serum concentrations of 23 POPs.

    RESULTS: There were statistically significant interactions between fat mass and POPs in predicting total mortality. In those with low POP concentrations, there was no obesity paradox; mortality increased with fat mass (hazard ratios about 2-3 in the highest vs lowest quintile of fat mass). However, consistent with an obesity paradox, these patterns completely disappeared in those with high POP concentrations. Compared with the lowest quintile of fat mass, statistically significantly lower mortality was observed in the elderly in the third to fifth quintiles of fat mass. In the case of polychlorinated biphenyls, the mortality in the highest quintile of fat mass was only one-fifth of that in the lowest quintile.

    CONCLUSION: These findings are consistent with our hypothesis that adipose tissue provides relatively safe storage of toxic lipophilic chemicals, a phenomenon that could explain the obesity paradox. Although weight loss may be beneficial among the obese elderly with low POP concentrations, weight loss in the obese elderly with higher serum concentrations of POPs may carry some risk.

  • 17.
    Islam, M. Shahidul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Sjöholm, Å.
    Emilsson, V.
    Fetal pancreatic islets express functional leptin receptors and leptin stimulates proliferation of fetal islet cells2000In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 24, no 10, p. 1246-1253Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Previous studies have demonstrated that leptin can stimulate proliferation of insulin-secreting tumor cell lines. The objective of this study was to characterize whether leptin could stimulate proliferation of primary beta-cells too. Since adult beta-cells have very limited capacity for replication, we examined the effect of leptin on islets of Langerhans obtained from fetal rats, in a tissue culture system. METHODS: Leptin receptor mRNA and c-fos mRNA were measured by RT-PCR. Proliferation of fetal rat islet cells was measured by a WST-1 colorimetric assay and [3H]-thymidine incorporation assay. RESULTS: Leptin stimulated proliferation of serum-deprived fetal rat islet cells, as indicated by increased formation of formazan dye from a tetrazolium salt WST-1. Leptin stimulated DNA synthesis in islet cells, as indicated by increased [3H]-thymidine incorporation into DNA. The effect of leptin on islet cell proliferation was on average 39-50% of the effect obtained with 10% fetal bovine serum. Leptin increased c-fos mRNA expression by 2.8-fold in isolated fetal islets after 30 min treatment. In fetal pancreatic islets, both the common extracellular portion (OB-R) and the intact long form (OB-Rb) of the leptin receptor were readily detected by reverse transcriptase polymerase chain reaction. CONCLUSION: Functional leptin receptors are expressed in pancreatic islet cells, as early as during the fetal stage of development of these microorgans. Leptin stimulates proliferation of fetal islet cells and might play a role in determining islet cell mass at birth.

  • 18.
    Jacobsson, J. A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Klovins, Janis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kapa, I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Danielsson, P
    Svensson, V
    Ridderstråle, M
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Marcus, C
    Fredriksson, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 11, p. 1730-1735Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits.

    RESULTS

    We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS.

    CONCLUSION

    These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.

  • 19.
    Jacobsson, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Moschonis, G
    Koumpitski, A
    Chrousos, G P
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Marcus, C
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children2012In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 1, p. 119-129Article in journal (Refereed)
    Abstract [en]

    Objective: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men.

    Design: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children.

    Results: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038).

    Conclusion: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.

  • 20. Johansson, K.
    et al.
    Sundström, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Marcus, C.
    Hemmingsson, E.
    Neovius, M.
    Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study2014In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 38, no 2, p. 279-284Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Concern exists regarding gallstones as an adverse event of very-low-calorie diets (VLCDs; <800 kcal per day). OBJECTIVE: To assess the risk of symptomatic gallstones requiring hospital care and/or cholecystectomy in a commercial weight loss program using VLCD or low-calorie diet (LCD). DESIGN: A 1-year matched cohort study of consecutively enrolled adults in a commercial weight loss program conducted at 28 Swedish centers between 2006 and 2009. A 3-month weight loss phase of VLCD (500 kcal per day) or LCD (1200-1500 kcal per day) was followed by a 9-month weight maintenance phase. Matching (1: 1) was performed by age, sex, body mass index, waist circumference and gallstone history (n = 3320: 3320). Gallstone and cholecystectomy data were retrieved from the Swedish National Patient Register. RESULTS: One-year weight loss was greater in the VLCD than in the LCD group (-11.1 versus -8.1 kg; adjusted difference, -2.8 kg, 95% CI -3.1 to -2.4; P<0.001). During 6361 person-years, 48 and 14 gallstones requiring hospital care occurred in the VLCD and LCD groups, respectively, (152 versus 44/10 000 person-years; hazard ratio, 3.4, 95% CI 1.8-6.3; P<0.001; number-needed-to-harm, 92, 95% CI 63-168; P<0.001). Of the 62 gallstone events, 38 (61%) resulted in cholecystectomy (29 versus 9; hazard ratio, 3.2, 95% CI 1.5-6.8; P = 0.003; number-needed-to-harm, 151, 95% CI 94-377; P<0.001). Adjusting for 3-month weight loss attenuated the hazard ratios, but the risk remained higher with VLCD than LCD for gallstones (2.5, 95% CI 1.3-5.1; P = 0.009) and became borderline for cholecystectomy (2.2, 95% CI 0.9-5.2; P = 0.08). CONCLUSION: The risk of symptomatic gallstones requiring hospitalization or cholecystectomy, albeit low, was 3-fold greater with VLCD than LCD during the 1-year commercial weight loss program.

  • 21.
    Kullberg, Joel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Frimmel, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Automated and reproducible segmentation of visceral and subcutaneous adipose tissue from abdominal MRI2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, p. 1806-1817Article in journal (Refereed)
  • 22. Li, X.
    et al.
    Lindquist, S.
    Chen, R.
    Myrnäs, T.
    Angsten, Gertrud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Olsson, T.
    Hernell, O.
    Depot-specific messenger RNA expression of 11 beta-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, no 5, p. 820-828Article in journal (Refereed)
    Abstract [en]

    Objective: To compare expression of messenger RNA (mRNA) coding for the cortisol regenerating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), and the adipocytokines leptin and resistin in paired biopsies of subcutaneous adipose tissue (SC) and omental adipose tissue (OM) from children. Design: Paired biopsies (SC and OM) were obtained from 54 children (age 0.17-16 years, body mass index (BMI) 12.5-28.3 kg/m(2), BMI standard deviation score (SDS) -2.5-4.5) and 16 adults (age 27-79 years, BMI 19-46 kg/m(2)) undergoing open abdominal surgery. mRNA levels of 11 beta-HSD1, leptin and resistin were measured using quantitative real-time polymerase chain reaction (PCR). Results: 11 beta-HSD1 mRNA level was higher in OM than in SC (P < 0.05), whereas leptin mRNA was higher in SC than in OM (P < 0.001). There was no difference in the resistin mRNA level between SC and OM. These results were consistent in children and adults. In children, 11 beta-HSD1 mRNA in SC was positively associated with BMI SDS (P < 0.05), whereas in OM it was positively associated with age (P < 0.05). The association between 11 beta-HSD1 expression and age remained significant after adjustment for BMI SDS and gender. Leptin mRNA was positively associated with BMI SDS (SC: P < 0.001, OM: P < 0.001) but not with age in children. In multiple regression analyses, including anthropometric variables and age, BMI SDS was independently associated with mRNA levels of 11 beta-HSD1 (P < 0.05) and leptin (P < 0.001) in SC. When normal weight and overweight children were analyzed separately, 11 beta-HSD1 mRNA levels were positively associated with leptin in OM in the overweight group (P < 0.05). Conclusion: There are depot-specific differences in mRNA levels of 11 beta-HSD1 and leptin in children and adults. The positive association of 11 beta-HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during growth. Increasing 11 beta-HSD1 and leptin mRNA in SC with increasing BMI SDS could suggest that the risk of metabolic consequences of obesity may be established early in life.

  • 23.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, F. Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vasoreactivity is rapidly improved in obese subjects after gastric bypass surgery2009In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 33, no 12, p. 1390-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. We investigated vasoreactivity in conduit and resistance arteries in morbidly obese subjects, and the effect of weight loss after gastric bypass surgery. METHODS: A total of 19 obese subjects (body mass index (BMI): 43.8+/-3.1 kg m(-2), 75% female, mean age 41 years) were investigated before surgery and after 1 and 12 months of surgery. Nineteen non-obese controls matched for age and gender were examined. Vasoreactivity was evaluated by ultrasound to measure flow-mediated dilation (FMD, evaluating a conduit vessel) and pulse-wave analysis with terbutaline provocation (change in reflectance index (RI), evaluating resistance vessels). RESULTS: Before surgery, the obese showed a low change in RI (18+/-12 vs 37+/-15% in controls, P=0.0001), but not significantly regarding FMD (7.9+/-6.4 vs 8.9+/-5.4% in controls). Surgery resulted in a weight loss of 9% at 1 month and 30% at 1 year. Change in RI markedly improved to 36+/-12% at 1 month (P=0.0001 vs baseline) and further to 44+/-11% at 1 year (P=0.014 vs 1 month). FMD did not change significantly. Heart rate and brachial artery diameter were reduced, with no significant change in blood pressure. The improvement in resistance vessel vasodilation, estimated as change in RI, was not correlated to changes in weight or measures of glucose and lipid metabolism. CONCLUSIONS: Obese patients showed impaired vasoreactivity in resistance arteries that was normalized already 1 month after gastric bypass surgery. The basis for this remarkable outcome, not significantly related to changes in body weight and metabolic variables, remains to be clarified.

  • 24.
    Lissner, L.
    et al.
    Section for Epidemiology and Community Medicine (EPSO), Department of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden.
    Wijnhoven, T. M. A.
    Division of Noncommunicable Diseases and Promoting Health Through the Life-Course, WHO Regional Office for Europe, UN City, Copenhagen, Denmark .
    Mehlig, K.
    Section for Epidemiology and Community Medicine (EPSO), Department of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden.
    Sjöberg, A.
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden.
    Kunesova, M.
    Obesity Management Centre, Institute of Endocrinology, Prague, Czech Republic.
    Yngve, Agneta
    Örebro universitet, Restaurang- och hotellhögskolan.
    Petrauskiene, A.
    Department of Preventive Medicine, Faculty of Public Health, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Duleva, V.
    Department of Food and Nutrition, National Center of Public Health and Analyses, Sofia, Bulgaria.
    Rito, A. I.
    Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
    Breda, J.
    Division of Noncommunicable Diseases and Promoting Health Through the Life-Course, WHO Regional Office for Europe, UN City, Copenhagen, Denmark.
    Socioeconomic inequalities in childhood overweight: heterogeneity across five countries in the WHO European Childhood Obesity Surveillance Initiative (COSI-2008)2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 5, p. 796-802Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Excess risk of childhood overweight and obesity occurring in socioeconomically disadvantaged families has been demonstrated in numerous studies from high-income regions, including Europe. It is well known that socioeconomic characteristics such as parental education, income and occupation are etiologically relevant to childhood obesity. However, in the pan-European setting, there is reason to believe that inequalities in childhood weight status may vary among countries as a function of differing degrees of socioeconomic development and equity.

    SUBJECTS AND METHODS: In this cross-sectional study, we have examined socioeconomic differences in childhood obesity in different parts of the European region using nationally representative data from Bulgaria, the Czech Republic, Lithuania, Portugal and Sweden that were collected in 2008 during the first round of the World Health Organization ( WHO) European Childhood Obesity Surveillance Initiative.

    RESULTS: Heterogeneity in the association between parental socioeconomic indicators and childhood overweight or obesity was clearly observed across the five countries studied. Positive as well as negative associations were observed between parental socioeconomic indicators and childhood overweight, with statistically significant interactions between country and parental indicators.

    CONCLUSIONS: These findings have public health implications for the WHO European Region and underscore the necessity to continue documenting socioeconomic inequalities in obesity in all countries through international surveillance efforts in countries with diverse geographic, social and economic environments. This is a prerequisite for universal as well as targeted preventive actions.

  • 25.
    Moraeus, L.
    et al.
    Department of Public Health and Community Medicine, Public Health Epidemiology Unit, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lissner, L.
    Department of Public Health and Community Medicine, Public Health Epidemiology Unit, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Yngve, Agneta
    Department of Biosciences and Nutrition, Unit for Public Health Nutrition, Karolinska Institutet, Stockholm, Sweden; 3Department of Health, Nutrition and Management, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
    Poortvliet, E.
    Department of Biosciences and Nutrition, Unit for Public Health Nutrition, Karolinska Institutet, Stockholm, Sweden; 3Department of Health, Nutrition and Management, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
    Al-Ansari, U.
    Department of Biosciences and Nutrition, Unit for Public Health Nutrition, Karolinska Institutet, Stockholm, Sweden; 3Department of Health, Nutrition and Management, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
    Sjöberg, A.
    Department of Public Health and Community Medicine, Public Health Epidemiology Unit, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Food and Nutrition, and Sport Science, University of Gothenburg, Gothenburg, Sweden.
    Multi-level influences on childhood obesity in Sweden: societal factors, parental determinants and child's lifestyle2012In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 7, p. 969-976Article in journal (Refereed)
    Abstract [en]

    Background: Swedish school children living in rural areas and in areas with low education are at excess risk of becoming overweight. This study examines influences of societal and individual characteristics (children and their parents) on prevalence of overweight and obesity, in a national sample of 7-9-year-old children.

    Method: Anthropometric and lifestyle data were collected in a nationally representative sample of 3636 Swedish children. Overweight and obesity (International Obesity Task Force (IOTF)) data were analyzed in relation to lifestyle factors, parental weight, education and breast-feeding.

    Results: The prevalence of overweight was 15.6% including 2.6% obese. Urbanization level and parental characteristics (weight status and education) were related to risk of overweight. Overall less favorable lifestyle characteristics were observed in rural areas and for children of low/medium educated mothers. Boys had greater risk of obesity in semi-urban and rural areas but this was not true for girls. For children's overweight, the living area effect was attenuated in multivariate analysis, while there was an association with origin of parents, high parental weight and medium maternal education. For obesity, the living area effect remained in boys while having two non-Nordic parents predicted obesity in girls. Parental weight status was associated with obesity in both girls and boys.

    Conclusion: Individual and societal factors influence children's weight status, and parental weight status is a strong determinant. Including overweight and obese parents in future health promoting interventions could be a strategy to prevent children from becoming overweight, but identifying those parents may prove difficult. To ensure reaching children with the greatest needs, targeting high risk areas might be a more effective approach.

  • 26.
    Nordhamn, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Södergren, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Olsson, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Reliability of anthropometric measurements in overweight and lean subjects:: consequences for corelations between anthropometric and other variable2000In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 24, no 5, p. 652-657Article in journal (Other academic)
    Abstract [en]

    OBJECTIVE

    To estimate the reliability of anthropometric measurements in overweight and lean subjects, and to examine the influence of this reliability on correlations to other variables, since low reliability leads to underestimation of correlations.

    DESIGN

    Replicate measurements by two observers in 26 overweight and 25 lean subjects measured at two occasions.

    MEASUREMENTS

    Sagittal abdominal diameter (SAD), waist circumference (waist), waist-to-hip ratio (W/H) and skinfold measurements.

    RESULTS

    Intra-class correlation coefficients (ICCs) for SAD and waist were higher than for W/H (0.98 vs 0.90, P<0.001, and 0.97 vs 0.90, P=0.001, respectively). For waist, the ICC was lower for overweight than for lean subjects (0.85 vs 0.95, P=0.030), but the ICC values were comparable for SAD and W/H (0.92 vs 0.95 and 0.78 vs 0.83, respectively). Intra-observer variations (IOV) for SAD and waist were lower than for W/H (coefficients of variation; 1.6%, 1.4% and 2.3%, respectively), as were intra-subject variations (ISV) (2.7%, 3.0% and 3.4%, respectively). ICC values ranged from 0.84 to 0.93 and were lower for overweight than for lean subjects for biceps, subscapular and umbilical skinfolds (P=0.031, P<0.001 and P=0.048, respectively). Coefficients of variations for skinfold measurements ranged between 7.3% and 16.0% for IOV and between 14.9% and 20.8% for ISV.

    CONCLUSIONS

    The low ICC values imply that correlations can be underestimated in overweight groups. We propose that, because of their higher reliability, SAD and waist have a higher predictive capacity for cardiovascular risk than W/H. SAD is the only measurement with high reliability in both weight groups and its use is recommended.

  • 27.
    Novak, Masuma
    et al.
    Umeå universitet, Allmänmedicin.
    Ahlgren, Christina
    Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Hammarström, Anne
    Umeå universitet, Allmänmedicin.
    A life-course approach in explaining social inequity in obesity among young adult men and women.2006In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 30, no 1, p. 191-200Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the cumulative influence of adverse behavioural, social, and psychosocial circumstances from adolescence to young adulthood in explaining social differences in overweight and obesity at age 30 years and if explanations differ by gender.

    Design: A 14-year longitudinal study with 96.4% response rate.

    Subject: Data from 547 men and 497 women from a town in north Sweden who were baseline examined at age 16 years and prospectively followed up to age 30 years.

    Measurements: Overweight and obesity were ascertained at ages 16 and 30 years. Occupation and education were used to measure socioeconomic status. The explanatory measurements were: age at menarche, smoking, physical activity, alcohol consumption, TV viewing, home and school environment, social support, social network, and work environment.

    Results: No gender or social difference in overweight was observed at age 16 years. At age 30 years, significantly more men than women (odds ratio (OR)¼2.81, 95% confidence interval (CI) 2.14–3.68) were overweight or obese. Educational level was associated with overweight at age 30 years, but not occupational class. Both men (OR¼1.55, 95% CI 1.10–2.19) and women (OR¼1.78, 95% CI 1.16–2.73) with low education (p11 years) were at risk of overweight. The factors that explained the educational gradient in overweight among men were low parental support in education during adolescence, and physical inactivity, alcohol consumption, and nonparticipation in any association during young adulthood. The educational gradient in overweight in women was explained mostly by adolescence factors, which include early age at menarche, physical inactivity, parental divorce, not being popular in school, and low school control. Restricted financial resource during young adulthood was an additional explanatory factor for women. All these factors were significantly more common among men and women with low education than with high education.

    Conclusion: Social inequities in overweight reflect the cumulative influence of multiple adverse circumstances experienced from adolescence to young adulthood. Underlying pathways to social inequity in overweight differ between men and women. Policy implications to reduce social inequity in overweight include reduction of social differences in health behaviours and social circumstances that take place at different life stages, particularly psychosocial circumstances during adolescence.

  • 28. Otten, J
    et al.
    Mellberg, C
    Ryberg, M
    Sandberg, S
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindahl, B
    Larsson, C
    Hauksson, J
    Olsson, T
    Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 5, p. 747-753Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD).

    SUBJECTS/METHODS: Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included.

    RESULTS: Liver fat decreased after 6 months by 64% (95% confidence interval: 54-74%) in the PD group and by 43% (27-59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25-75%) in the PD group and 49% (27-71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes.

    CONCLUSIONS: A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.

  • 29.
    Petrus, P
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Edholm, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dahlman, I
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Arner, P
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Rydén, M
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 8, p. 1295-1298Article in journal (Refereed)
    Abstract [en]

    Cardiometabolic diseases are primarily linked to enlarged visceral adipose tissue (VAT). However, some data suggest heterogeneity within the subcutaneous adipose tissue (SAT) depot with potential metabolic differences between the superficial SAT (sSAT) and deep SAT (dSAT) compartments. We aimed to investigate the heterogeneity of these three depots with regard to fatty acid (FA) composition and gene expression. Adipose tissue biopsies were collected from 75 obese women undergoing laparoscopic gastric bypass surgery. FA composition and gene expression were determined with gas chromatography and quantitative real-time-PCR, respectively. Stearoyl CoA desaturase-1 (SCD-1) activity was estimated by product-to-precursor FA ratios. All polyunsaturated FAs (PUFA) with 20 carbons were consistently lower in VAT than either SAT depots, whereas essential PUFA (linoleic acid, 18:2n-6 and α-linolenic acid, 18:3n-3) were similar between all three depots. Lauric and palmitic acid were higher and lower in VAT, respectively. The SCD-1 product palmitoleic acid as well as estimated SCD-1 activity was higher in VAT than SAT. Overall, there was a distinct association pattern between lipid metabolizing genes and individual FAs in VAT. In conclusion, SAT and VAT are two distinct depots with regard to FA composition and expression of key lipogenic genes. However, the small differences between sSAT and dSAT suggest that FA metabolism of SAT is rather homogenous.

  • 30.
    Rodriguez, Alina
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Miettunen, J
    Henriksen, TB
    Olsen, J
    Obel, C
    Taanila, A
    Ebeling, H
    Linnet, KM
    Moilanen, I
    Järvelin, MR
    Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 3, p. 550-557Article in journal (Refereed)
    Abstract [en]

    Objectives: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. Design: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. Methods: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. Results: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. Conclusions: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.

  • 31.
    Rogers, P. J.
    et al.
    Univ Bristol, Sch Expt Psychol, Bristol, Avon, England..
    Hogenkamp, Pleunie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    de Graaf, C.
    Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands..
    Higgs, S.
    Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England..
    Lluch, A.
    RD, Ctr Daniel Carasso, Danone Res, Palaiseau, France..
    Ness, A. R.
    Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Unit Nutr Diet & Li, Level 3, Bristol, Avon, England.;Univ Bristol, Level 3, Bristol, Avon, England.;Univ Bristol, Univ Hosp Bristol Educ Ctr, Sch Oral & Dent Sci, Level 3, Bristol, Avon, England..
    Penfold, C.
    Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Unit Nutr Diet & Li, Level 3, Bristol, Avon, England.;Univ Bristol, Level 3, Bristol, Avon, England.;Univ Bristol, Univ Hosp Bristol Educ Ctr, Sch Oral & Dent Sci, Level 3, Bristol, Avon, England..
    Perry, R.
    Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Unit Nutr Diet & Li, Level 3, Bristol, Avon, England.;Univ Bristol, Level 3, Bristol, Avon, England.;Univ Bristol, Univ Hosp Bristol Educ Ctr, Sch Oral & Dent Sci, Level 3, Bristol, Avon, England..
    Putz, P.
    ILSI Europe Aisbl, European Branch, Ave E Mounier 83,Box 6, B-1200 Brussels, Belgium..
    Yeomans, M. R.
    Univ Sussex, Sch Psychol, Brighton, E Sussex, England..
    Mela, D. J.
    Unilever Res Labs, Vlaardingen, Netherlands..
    Does low-energy sweetener consumption affect energy intake and body weight?: A systematic review, including meta-analyses, of the evidence from human and animal studies2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 3, p. 381-394Article, review/survey (Refereed)
    Abstract [en]

    By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific 'learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (-0.002 kg m(-2) per year, 95% confidence interval (CI) -0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (-94 kcal, 95% CI -122 to -66), with no difference versus water (-2 kcal, 95% CI -30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; -1.35 kg, 95% CI -2.28 to -0.42), and a similar relative reduction in BW versus water (three comparisons; -1.24 kg, 95% CI -2.22 to -0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.

  • 32. Ruof, J
    et al.
    Golay, A
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Collin, C
    Lentz, J
    Maetzel, A
    Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland2005In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 29, no 5, p. 517-523Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes.

    METHODS: Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results.

    RESULTS: A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of euro14 000 in Sweden and euro13 600 in Switzerland.

    CONCLUSION: The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.

  • 33. Steffen, L M
    et al.
    Vessby, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Jacobs, D R
    Steinberger, J
    Moran, A
    Hong, C-P
    Sinaiko, A R
    Serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities are related to overweight and cardiovascular risk factors in adolescents2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 8, p. 1297-1304Article in journal (Refereed)
    Abstract [en]

    Aim/hypothesis: The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents. Methods: The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta 9 DA 16: 0/16: 1, Delta 6 DA 20: 3, n6/18: 2, n6 (PL) or 18: 3, n6/18: 2, n6 (CE), and Delta 5 DA 20: 4, n6/20: 3, n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity. Results: Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and D6 DA and D5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P < ;= 0.01). Dihomo-gamma-linolenic acid was positively related to BMI, waist, insulin, and triglycerides, and inversely related to high-density lipoprotein-cholesterol levels (P < ;= 0.01). D6 DA was adversely associated with most of the risk factors (P < ;= 0.01), whereas triglycerides and fasting insulin were beneficially related to D5 DA (P < ;= 0.01). Conclusion: These findings support those observed in adults, that factors, such as type of dietary fat, physical activity, and obesity, may influence fatty acid metabolism and are important in the development of adverse CVD risk factors as early as adolescence.

  • 34.
    Svensson, Viktoria
    et al.
    Karolinska Institutet, Department of Clinical Science.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Danielsson, Pernilla
    Karolinska Institutet, Department of Clinical Science.
    Sobko, T
    Karolinska Institutet, Department of Clinical Science.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Marcus, Claude
    Karolinska Institutet, Department of Clinical Science.
    Associations between severity of obesity in childhood and adolescence, obesity onset andparental BMI: a longitudinal cohort study2011In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 35, no 1, p. 46-52Article in journal (Refereed)
    Abstract [en]

    Objective: To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents. Design:Longitudinal cohort study. Subjects:Obese children (n=231) and their parents (n=462) from the Swedish National Childhood Obesity Centre. Methods: Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment. Results: For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P=0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P<0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents. Conclusion: The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing.

  • 35.
    Sällman Almén, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ameur, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kalnina, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Moschonis, G
    Juhlin, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bringeland, Nathalie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hedberg, Lidwig A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ignatovica, V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chrousos, G P
    Manios, Y
    Klovins, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Marcus, C
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children.2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 3, p. 424-431Article in journal (Refereed)
    Abstract [en]

    Background:The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index.Methods:In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD).Results:The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012).Conclusions:This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.

  • 36. Tierney, A C
    et al.
    McMonagle, J
    Shaw, D I
    Gulseth, H L
    Helal, O
    Saris, W H M
    Paniagua, J A
    Gołąbek-Leszczyñska, I
    Defoort, C
    Williams, C M
    Karsltröm, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dembinska-Kiec, A
    López-Miranda, J
    Blaak, E E
    Drevon, C A
    Gibney, M J
    Lovegrove, J A
    Roche, H M
    Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome-LIPGENE: a European randomized dietary intervention study2011In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 35, no 6, p. 800-809Article in journal (Refereed)
    Abstract [en]

    Background:Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS.Objective:This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS.Design:A free-living, single-blinded dietary intervention study.Subjects and Methods:MetS subjects (n=417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined.Results:In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P<0.01), particularly in men.Conclusion:There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

  • 37.
    Wiemerslage, L
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Islam, R
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    van der Kamp, C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cao, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ence-Eriksson, F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Castillo, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, A L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bandstein, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, L S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Perland, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Gustavsson, V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, H
    Schürmann, A
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 6, p. 990-994Article in journal (Refereed)
    Abstract [en]

    We investigated five methylation markers recently linked to body-mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus, and frontal gyri, some of which have been previously associated to food signaling, obesity, or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity, and genetic differences.

1 - 37 of 37
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