| Summary: | Gudrun Valgerdur Skuladottir,1,2 Harpa Oskarsdottir1 Claudia Pisanu,2,3 Marcus Sjödin,4 Johan Lindberg,4 Jessica Mwinyi,2 Helgi Birgir Schiöth2 1Department of Physiology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 2Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden; 3Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy; 4Swetox, Karolinska Institutet, Unit of Toxicological Sciences, Södertälje, Sweden Purpose: Dietary macronutrient composition, stearoyl-CoA desaturase (SCD) activity indices, and primary bile acid (BA) concentrations are among the factors that have been associated with lipid metabolism and contributed to obesity. We investigated the association between the polymorphic expression of the fat mass and obesity-associated (FTO) gene and its relationship with SCD activity indices and primary BA concentrations after a low-fat meal.Subjects and methods: Blood plasma samples were collected from 56 young (20–36 years) healthy subjects with different rs9939609 FTO genotypes. Fasting and post-meal (2 hours after a low-fat breakfast) blood samples were collected on the subsequent morning for the analysis of DNA methylation, SCD activity indices (product-to-precursor fatty acid ratios; 16:1n-7/16:0 and 18:1n-9/18:0), and chenodeoxycholic acid (CDCA) and cholic acid (CA) concentrations. Expression of lipogenic genes was investigated post-meal to assess the relationship between the CDCA and CA concentrations and mRNA levels of lipogenic genes.Results: The FTO AA (obesity risk) genotype group (n=18) had higher (P<0.05) post-meal SCD-16 activity index than the FTO TT (wild type) genotype group (n=26). In both the FTO TT (n=16) and AA (n=8) genotype groups, the post-meal concentrations of CDCA and CA were lower (P<0.05) compared with the fasted state. No difference in BA concentrations between the FTO TT and AA genotype groups in both meal states was observed. After adjusting for the body mass index, the highest 50% post-meal concentrations of CA were inversely (P=0.010) correlated with the level of mRNA SCD expression.Conclusion: FTO AA carriers may be at a higher risk for obesity through higher SCD activity in a low-fat diet environment. This effect may be partly pronounced by very low CA concentrations. Keywords: rs9939609, dietary fat, SCD activity, cholic acid, lipid metabolism
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