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Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.ORCID iD: 0000-0003-2256-6972
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Molekylär geriatrik)
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2007 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 15, no 7, 1732-1740 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme A-desaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans.

RESEARCH METHODS AND PROCEDURES:

The study population was 1143 elderly Swedish men taking part of a population-based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis.

RESULTS:

Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (beta)=1.19, p=0.007] and waist circumference (beta=-4.4, p=0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference.

CONCLUSION:

This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.

Place, publisher, year, edition, pages
2007. Vol. 15, no 7, 1732-1740 p.
Keyword [en]
stearoyl-coenzyme A-desaturase, waist circumference, insulin sensitivity, single-nucleotide polymorphism
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96455DOI: 10.1038/oby.2007.206ISI: 000248242900014OAI: oai:DiVA.org:uu-96455DiVA: diva2:171032
Available from: 2007-11-16 Created: 2007-11-16 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Fatty Acid Desaturase Activities in Metabolic Syndrome and Cardiovascular Disease: Special Reference to Stearoyl-CoA-Desaturase and Biomarkers of Dietary Fat
Open this publication in new window or tab >>Fatty Acid Desaturase Activities in Metabolic Syndrome and Cardiovascular Disease: Special Reference to Stearoyl-CoA-Desaturase and Biomarkers of Dietary Fat
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios.

In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice.

This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 292
Keyword
Nutrition, Fatty acids, Dietary fat, Biomarker, Metabolic Syndrome, Mortality, Obesity, Insulin Sensitivity, Epidemiology, Estimated desaturase activities, Stearoyl-CoA-desaturase, delta-6-desaturase, delta-5-desaturase, Single Nucleotide Polymorphism, Dietary Intervention, Rapeseed oil, Saturated fat, SCD1, Näringslära
Identifiers
urn:nbn:se:uu:diva-8312 (URN)978-91-554-7025-8 (ISBN)
Public defence
2007-12-07, IV, Universitetshuset, Uppsala, 09:15
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Supervisors
Available from: 2007-11-16 Created: 2007-11-16Bibliographically approved

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Warensjö, EvaIngelsson, ErikLundmark, PerLannfelt, LarsSyvänen, Ann-ChristineVessby, BengtRisérus, Ulf

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