Single Nucleotide Polymorphisms in Close Proximity to the Fibroblast Growth Factor 21 (FGF21) Gene Found to Be Associated with Sugar Intake in a Swedish Population

Abstract

Hereditary mechanisms are partially responsible for individual differences in sensitivity to and the preference for sweet taste. The primary aim of this study was to examine the associations between 10 genetic variants and the intake of total sugar, added sugar, and sugars with sweet taste (i.e., monosaccharides and sucrose) in a middle-aged Swedish population. Two single nucleotide polymorphisms (SNPs) within the Fibroblast grow factor 21 (FGF21) gene, seven top hits from a genome-wide association study (GWAS) on total sugar intake, and one SNP within the fat mass and obesity associated (FTO) gene (the only SNP reaching GWAS significance in a previous study), were explored in relation to various forms of sugar intake in 22,794 individuals from the Malmö Diet and Cancer Study, a population-based cohort for which data were collected between 1991–1996. Significant associations (p = 6.82 × 10−7 − 1.53 × 10−3) were observed between three SNPs (rs838145, rs838133, and rs8103840) in close relation to the FGF21 gene with high Linkage Disequilibrium, and all the studied sugar intakes. For the rs11642841 within the FTO gene, associations were found exclusively among participants with a body mass index ≥ 25 (p < 5 × 10−3). None of the remaining SNPs studied were associated with sugar intake in our cohort. A further GWAS should be conducted to identify novel genetic variants associated with the intake of sugar.

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

“…These interferences can be localized in the gut, but others have systemic effects, leading, for example, to IR and can be related to the MetS risk factors [ 99 ]. Furthermore, diet regulates some organokines, such as FGF-21 [ 100 ].…”

Liver Fibroblast Growth Factor 21 (FGF21) is Required for the Full Anorectic Effect of the Glucagon-Like Peptide-1 Receptor Agonist Liraglutide in Male Mice fed High Carbohydrate Diets

“…FGF21 mediates liraglutide-induced weight loss specifically in the context of highcarbohydrate diets. Since FGF21 suppresses carbohydrate intake and sweet preference in rodents 28,29 and has been associated with these phenotypes in humans [45][46][47][48][49][50] , we hypothesized that FGF21 contributes specifically to a reduction in body weight by liraglutide in the presence of high-carbohydrate diets. To test this hypothesis, we placed control and Liv Fgf21-/mice on calorically matched, low-fat diets with either low (LC) or high carbohydrate (HC) content (30%, LC and 70%, HC, respectively) for 4 weeks followed by a 2-week treatment with vehicle or liraglutide while mice remained on the respective diet.…”

“…These findings may be clinically relevant since they raise the testable hypothesis that dietary carbohydrate content can modify the effectiveness of GLP-1RA as weight loss drugs. Moreover, since several variants in the hFGF21 gene locus have been associated with effects on carbohydrate intake and sweet preference in humans [45][46][47][48][49][50] , results…”

Fibroblast growth factor-21 is required for weight loss induced by the glucagon-like peptide-1 receptor agonist liraglutide in male mice fed high carbohydrate diets

“…Since FGF21 suppresses carbohydrate intake and sweet preference in rodents [ 28 , 29 ] and has been associated with these phenotypes in humans [ [47] , [48] , [49] , [50] , [51] , [52] ], we hypothesized that FGF21 contributes specifically to a reduction in body weight by liraglutide in the presence of high carbohydrate diets. To test this hypothesis, we placed control and Liv Fgf21−/− mice on calorically matched, low fat diets with either low (LC) or high carbohydrate (HC) content (30%, LC and 70%, HC, respectively) for 4 weeks followed by a 2-week treatment with vehicle or liraglutide while mice remained on their respective diet.…”