Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome |
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| Authors: | Catherine M. Phillips Louisa Goumidi Sandrine Bertrais Martyn R. Field L. Adrienne Cupples Jose M. Ordovas Catherine Defoort Julie A. Lovegrove Christian A. Drevon Michael J. Gibney Ellen E. Blaak Beata Kiec-Wilk Britta Karlstrom Jose Lopez-Miranda Ross McManus Serge Hercberg Denis Lairon Richard Planells Helen M. Roche |
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| Affiliation: | 1. Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, and Institute of Food and Health, University College Dublin, Ireland;2. INSERM 476, Lipid nutrients and prevention of metabolic diseases, INRA, 1260, Université de la Méditerranée, Faculté de Médecine, 27 Bd Jean Moulin, Marseille, France;4. INSERM U557, INRA:CNAM, Université Paris 13, Bobigny, France;7. Hitachi Dublin Laboratory, Dublin, Ireland;11. Boston University School of Public Health, Boston, MA;8. Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA;71. Hugh Sinclair Unit of Human Nutrition, Department of Food Biosciences, Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, UK;112. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway;84. Institute of Food and Health, University College Dublin, Ireland;77. Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht, The Netherlands;1111. Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15A, Krakow, Poland;88. Department of Public Health and Caring Sciences/Clinical Nutrition and Metabolism, Uppsala University, Uppsala Science Park, 751 85 Uppsala, Sweden;771. Lipid and Atherosclerosis Unit, Department of Medicine, Reina Sofia University Hospital, School of Medicine, University of Cordoba, Spain;11112. Institute of Molecular Medicine, Trinity College Dublin, Ireland |
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| Abstract: | Long-chain acyl CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and triacylglycerol (TAG) synthesis. Disturbance of these pathways may result in dyslipidemia and insulin resistance, hallmarks of the metabolic syndrome (MetS). Dietary fat is a key environmental factor that may interact with genetic determinants of lipid metabolism to affect MetS risk. We investigated the relationship between ACSL1 polymorphisms (rs4862417, rs6552828, rs13120078, rs9997745, and rs12503643) and MetS risk and determined potential interactions with dietary fat in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1,754). GG homozygotes for rs9997745 had increased MetS risk {odds ratio (OR) 1.90 [confidence interval (CI) 1.15, 3.13]; P = 0.01}, displayed elevated fasting glucose (P = 0.001) and insulin concentrations (P = 0.002) and increased insulin resistance (P = 0.03) relative to the A allele carriers. MetS risk was modulated by dietary fat, whereby the risk conferred by GG homozygosity was abolished among individuals consuming either a low-fat (<35% energy) or a high-PUFA diet (>5.5% energy). In conclusion, ACSL1 rs9997745 influences MetS risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions. |
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| Keywords: | genetic polymorphisms insulin resistance fatty acid metabolism PUFA |
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