uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 11) Show all publications
Lundström, E., Ljungberg, J., Andersson, J., Manell, H., Strand, R., Forslund, A., . . . Kullberg, J. (2019). Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents. Pediatric Obesity, 14(9), Article ID e12531.
Open this publication in new window or tab >>Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
Show others...
2019 (English)In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 14, no 9, article id e12531Article in journal (Refereed) Published
Abstract [en]

Background

Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.

Objectives

To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes.

Methods

In 143 subjects (10‐20 years), MRI estimates of BAT were assessed as cervical‐supraclavicular adipose tissue (sBAT) fat fraction (FF) and T*2 from water‐fat MRI. FF and T*2 of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist‐to‐height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests.

Results

sBAT FF and T*2 correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T*2, correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF.

Conclusions

The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT T*2 might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T*2 quantification.

Keywords
adolescent, brown adipose tissue, glucose metabolism, magnetic resonance imaging
National Category
Pediatrics Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-380052 (URN)10.1111/ijpo.12531 (DOI)000482155600007 ()31290284 (PubMedID)
Funder
Swedish Heart Lung Foundation, 2170492Swedish Research Council, 2016-01040EU, FP7, Seventh Framework Programme, 279153
Available from: 2019-07-09 Created: 2019-03-22 Last updated: 2019-10-23Bibliographically approved
Andersson, J., Lundström, E., Engström, M., Lubberink, M., Ahlström, H. & Kullberg, J. (2019). Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI. Scientific Reports, 9, Article ID 12358.
Open this publication in new window or tab >>Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
Show others...
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed) Published
Abstract [en]

Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

Keywords
brown adipose tissue, 18F-FDG positron emission tomography, infrared thermography, magnetic resonance imagingm PET/MRI, water–fat signal separation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-390410 (URN)10.1038/s41598-019-48879-7 (DOI)000482564800014 ()31451711 (PubMedID)
Funder
Swedish Research Council, 2016-01040Swedish Heart Lung Foundation, 2170492EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-10-18Bibliographically approved
Motiani, P., Teuho, J., Saari, T., Virtanen, K. A., Honkala, S. M., Middelbeek, R. J., . . . Nuutila, P. (2019). Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity. OASE : tijdschrift voor architectuur, 5(3), 258-272
Open this publication in new window or tab >>Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity
Show others...
2019 (English)In: OASE : tijdschrift voor architectuur, ISSN 2451-8476, E-ISSN 2055-2238, Vol. 5, no 3, p. 258-272Article in journal (Refereed) Published
Abstract [en]

Introduction New strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold-stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites. Methods Healthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m(-2); VO2 max 39 [7.6] mL min(-1) kg(-1)) participated in a 6-week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [F-18]fluorodeoxyglucose positron emission tomography-magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico-thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy. Results Cold exposure increased supraclavicular BAT GU by threefold (p < 0.001), energy expenditure by 59% (p < 0.001) and plasma fatty acids (p < 0.01). Exercise training had no effect on cold-induced GU in BAT or neck muscles. Training increased aerobic capacity (p = 0.01) and decreased visceral fat (p = 0.02) and cervico-thoracic BAT mass (p = 0.003). Additionally, training decreased very low-density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high-density lipoprotein (p = 0.04). Conclusions Although exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
Brown adipose tissue, exercise training, glucose uptake, nor-epinephrine, positron emission tomography
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-390601 (URN)10.1002/osp4.330 (DOI)000472584400008 ()31275600 (PubMedID)
Funder
Academy of Finland, 307402Academy of Finland, 292839Academy of Finland, 269977
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved
Kjellberg, E., Roswall, J., Andersson, J., Bergman, S., Karlsson, A.-K., Svensson, P.-A., . . . Dahlgren, J. (2019). Metabolic Risk Factors Associated with Visceral and Subcutaneous Adipose Tissue in a Sex-Specific Manner in Seven-Year-Olds. Obesity, 27(6), 982-988
Open this publication in new window or tab >>Metabolic Risk Factors Associated with Visceral and Subcutaneous Adipose Tissue in a Sex-Specific Manner in Seven-Year-Olds
Show others...
2019 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 27, no 6, p. 982-988Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: This study aimed to investigate how visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes were associated with metabolic risk factors in 7-year-old children.

METHODS: A total of 81 children (52% girls) from a Swedish birth cohort were studied. At 6 years of age, anthropometric data, fasting insulin, glucose, cholesterol, and blood pressure were collected on 53 children with normal weight and 28 children with overweight or obesity, and insulin resistance was estimated. At 7 years of age, magnetic resonance imaging quantified VAT and SAT. Sex and regression analyses were conducted.

RESULTS: SAT was more strongly associated with metabolic risk factors than VAT. The associations between VAT and metabolic risk factors were stronger in girls (P < 0.05). When VAT was adjusted for birth weight and maternal BMI and education, it accounted for 51% of insulin variance (β = 11.72; P = 0.001) but only in girls. The key finding of this study was that adjusted SAT accounted for 63% of the fasting insulin variance in girls (β = 2.76; P < 0.001). Waist circumference was the best anthropometric marker for insulin resistance.

CONCLUSIONS: Insulin resistance was associated with abdominal adipose tissue and its associated metabolic risk factors in children as young as 7 years old.

National Category
Endocrinology and Diabetes Nutrition and Dietetics Pediatrics
Identifiers
urn:nbn:se:uu:diva-382942 (URN)10.1002/oby.22453 (DOI)000468798100018 ()31004397 (PubMedID)
Funder
Swedish Research Council, 2016-01040Swedish Research Council, 2013-2003Swedish Nutrition Foundation (SNF)
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-24Bibliographically approved
Andersson, J., Roswall, J., Kjellberg, E., Ahlström, H., Dahlgren, J. & Kullberg, J. (2019). MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume. Magnetic Resonance Imaging, 58, 135-142
Open this publication in new window or tab >>MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume
Show others...
2019 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 58, p. 135-142Article in journal (Refereed) Published
Abstract [en]

Context: Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children.

Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured.

Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01).

Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2019
Keywords
Brown adipose tissue, Magnetic resonance imaging, Adiposity, Osteocalcin, Muscle volume, Quantitative MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-380416 (URN)10.1016/j.mri.2019.02.001 (DOI)000461412300018 ()30742901 (PubMedID)
Funder
Swedish Research Council, 2013-3013Swedish Research Council, 2016-01040Region Västra Götaland
Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-08-14Bibliographically approved
Andersson, J., Ahlström, H. & Kullberg, J. (2019). Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks. Magnetic Resonance in Medicine, 82(3), 1177-1186
Open this publication in new window or tab >>Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks
2019 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 82, no 3, p. 1177-1186Article in journal (Refereed) Published
Abstract [en]

Purpose: To perform and evaluate water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks.

Methods: Whole‐body gradient echo scans of 240 subjects, each consisting of 5 bipolar echoes, were used. Reference fat fraction maps were created using a conventional method. Convolutional neural networks, more specifically 2D U‐nets, were trained using 5‐fold cross‐validation with 1 or several echoes as input, using the squared difference between the output and the reference fat fraction maps as the loss function. The outputs of the networks were assessed by the loss function, measured liver fat fractions, and visually. Training was performed using a graphics processing unit (GPU). Inference was performed using the GPU as well as a central processing unit (CPU).

Results: The loss curves indicated convergence, and the final loss of the validation data decreased when using more echoes as input. The liver fat fractions could be estimated using only 1 echo, but results were improved by use of more echoes. Visual assessment found the quality of the outputs of the networks to be similar to the reference even when using only 1 echo, with slight improvements when using more echoes. Training a network took at most 28.6 h. Inference time of a whole‐body scan took at most 3.7 s using the GPU and 5.8 min using the CPU.

Conclusion: It is possible to perform water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks. Separation was possible using only 1 echo, although using more echoes improved the results.

Keywords
Dixon, convolutional neural network, deep learning, magnetic resonance imaging, neural network, water-fat separation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-382933 (URN)10.1002/mrm.27786 (DOI)000485077600026 ()31033022 (PubMedID)
Funder
Swedish Research Council, 2016-01040
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-10-15Bibliographically approved
Kjellberg, E., Roswall, J., Andersson, J., Bergman, S., Kullberg, J. & Dahlgren, J. (2018). IGF-I at Four Months Associates to Visceral and Subcutaneous Adipose Tissue at 7 Years of Age. Hormone Research in Paediatrics, 90, 93-93
Open this publication in new window or tab >>IGF-I at Four Months Associates to Visceral and Subcutaneous Adipose Tissue at 7 Years of Age
Show others...
2018 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 90, p. 93-93Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2018
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-368675 (URN)000445204100181 ()
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Andersson, J., Ahlström, H. & Kullberg, J. (2018). Water-fat separation incorporating spatial smoothing is robust to noise. Magnetic Resonance Imaging, 50, 78-83, Article ID S0730-725X(18)30040-7.
Open this publication in new window or tab >>Water-fat separation incorporating spatial smoothing is robust to noise
2018 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 50, p. 78-83, article id S0730-725X(18)30040-7Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To develop and evaluate a noise-robust method for reconstruction of water and fat images for spoiled gradient multi-echo sequences.

METHODS: The proposed method performs water-fat separation by using a graph cut to minimize an energy function consisting of unary and binary terms. Spatial smoothing is incorporated to increase robustness to noise. The graph cut can fail to find a solution covering the entire image, in which case the relative weighting of the unary term is iteratively increased until a complete solution is found. The proposed method was compared to two previously published methods. Reconstructions were performed on 16 cases taken from the 2012 ISMRM water-fat reconstruction challenge dataset, for which reference reconstructions were provided. Robustness towards noise was evaluated by reconstructing images with different levels of noise added. The percentage of water-fat swaps were calculated to measure performance.

RESULTS: At low noise levels the proposed method produced similar results to one of the previously published methods, while outperforming the other. The proposed method significantly outperformed both of the previously published methods at moderate and high noise levels.

CONCLUSION: By incorporating spatial smoothing, an increased robustness towards noise is achieved when performing water-fat reconstruction of spoiled gradient multi-echo sequences.

Keywords
Chemical shift imaging, Dixon, Graph cuts, Multi-scale, Quadratic pseudo-Boolean optimization, Water-fat separation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-347450 (URN)10.1016/j.mri.2018.03.015 (DOI)000434750700011 ()29601865 (PubMedID)
Funder
Swedish Research Council, 2016-01040
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-08-14Bibliographically approved
Honka, M.-J., Bucci, M., Andersson, J., Huovinen, V., Guzzardi, M. A., Sandboge, S., . . . Nuutila, P. (2016). Resistance training enhances insulin suppression of endogenous glucose production in elderly women. Journal of applied physiology, 120(6), 633-639
Open this publication in new window or tab >>Resistance training enhances insulin suppression of endogenous glucose production in elderly women
Show others...
2016 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 6, p. 633-639Article in journal (Refereed) Published
Abstract [en]

An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [F-18] fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [ from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) mu mol.kg body wt(-1).min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) mu mol.kg body wt(-1).min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training.

Keywords
liver, intra-abdominal fat, insulin resistance, resistance training, aging
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-286665 (URN)10.1152/japplphysiol.00950.2015 (DOI)000372061000008 ()26744506 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 278603
Available from: 2016-04-27 Created: 2016-04-21 Last updated: 2018-01-10Bibliographically approved
Bucci, M., Huovinen, V., Guzzardi, M. A., Koskinen, S., Raiko, J. R., Lipponen, H., . . . Nuutila, P. (2016). Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers.. Diabetologia, 59(1), 77-86
Open this publication in new window or tab >>Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers.
Show others...
2016 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 1, p. 77-86Article in journal (Refereed) Published
Abstract [en]

AIMS/HYPOTHESIS: Maternal obesity predisposes offspring to adulthood morbidities, including type 2 diabetes. Type 2 diabetes and insulin resistance have been associated with shortened telomere length. First, we aimed to investigate whether or not maternal obesity influences insulin sensitivity and its relationship with leucocyte telomere length (LTL) in elderly women. Second, we tested whether or not resistance exercise training improves insulin sensitivity in elderly frail women.

METHODS: Forty-six elderly women, of whom 20 were frail offspring of lean/normal weight mothers (OLM, BMI ≤26.3 kg/m(2)) and 17 were frail offspring of overweight/obese mothers (OOM, BMI ≥28.1 kg/m(2)), were studied before and after a 4 month resistance training (RT) intervention. Muscle insulin sensitivity of glucose uptake was measured using (18)F-fluoro-2-deoxyglucose and positron emission tomography with computed tomography during a hyperinsulinaemic-euglycaemic clamp. Muscle mass and lipid content were measured using magnetic resonance and LTL was measured using real-time PCR.

RESULTS: The OOM group had lower thigh muscle insulin sensitivity compared with the OLM group (p = 0.048) but similar whole body insulin sensitivity. RT improved whole body and skeletal muscle insulin sensitivity in the OOM group only (p = 0.004 and p = 0.013, respectively), and increased muscle mass in both groups (p < 0.01). In addition, in the OOM group, LTL correlated with different thigh muscle groups insulin sensitivity (ρ ≥ 0.53; p ≤ 0.05). Individuals with shorter LTL showed a higher increase in skeletal muscle insulin sensitivity after training (ρ ≥ -0.61; p ≤ 0.05).

CONCLUSIONS/INTERPRETATION: Maternal obesity and having telomere shortening were associated with insulin resistance in adult offspring. A resistance exercise training programme may reverse this disadvantage among offspring of obese mothers.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01931540.

Keywords
Computed tomography; Elderly; Hyperinsulinaemic-euglycaemic clamp; Insulin sensitivity; Magnetic resonance; Maternal obesity; Positron emission tomography; Resistance training; Telomere shortening
National Category
Medical and Health Sciences Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-266505 (URN)10.1007/s00125-015-3780-8 (DOI)000365804500010 ()26486356 (PubMedID)
Funder
EU, European Research Council, 278603
Available from: 2015-11-10 Created: 2015-11-10 Last updated: 2017-12-01Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6477-2331

Search in DiVA

Show all publications