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Nutrients 2018, 10(11), 1791; https://doi.org/10.3390/nu10111791

Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity

1
The George Institute for Global Health, University of New South Wales, Sydney, NSW 2042, Australia
2
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, 751 22 Uppsala, Sweden
3
Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK
4
The Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK
5
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
6
Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA
7
Stanford Diabetes Research Center, Stanford University, Stanford, CA 94305, USA
8
Department of Medical Sciences, Molecular Epidemiology, Uppsala University, 751 85 Uppsala, Sweden
9
Li Ka Shing Centre for Health Information and Discovery, The Big Data Institute, University of Oxford, Oxford OX3 7LF, UK
10
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, 751 85 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Received: 16 October 2018 / Revised: 13 November 2018 / Accepted: 14 November 2018 / Published: 17 November 2018
(This article belongs to the Special Issue Fatty Acids and Cardiometabolic Health)
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Abstract

Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of δ-5-desaturase (D5D), δ-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 × 10−70) and adipose tissue (p = 1.1 × 10−27). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 × 10−67; PDXDCI, p = 4.8 × 10−8; and near MC4R, p = 3.7 × 10−8) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 × 10−19). Genetic variants near MC4R were associated with IS (p = 3.8 × 10−3). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS. View Full-Text
Keywords: fatty acid; desaturase; Genome-wide association study (GWAS); Insulin sensitivity; adipose tissue; cholesterol ester fatty acid; desaturase; Genome-wide association study (GWAS); Insulin sensitivity; adipose tissue; cholesterol ester
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Marklund, M.; Morris, A.P.; Mahajan, A.; Ingelsson, E.; Lindgren, C.M.; Lind, L.; Risérus, U. Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity. Nutrients 2018, 10, 1791.

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