No Influence of the Fat Mass and Obesity-Associated Gene rs9939609 Single Nucleotide Polymorphism on Blood Lipids in Young Males.

James L Dorling,James A King,David J Stensel,Rachel L Batterham,Fernanda R Goltz,Andrea Pucci,Alice E Thackray

doi:10.3390/nu12123857

Abstract

The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (−1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0–5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) −0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI −0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI −0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI −6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations.

Highlights

At the fat-mass and obesity-associated gene (FTO) rs9939609 single nucleotide polymorphism (SNP), carriers of the obesity-risk A-allele present a higher risk of obesity compared to homozygousNutrients 2020, 12, 3857; doi:10.3390/nu12123857 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 3857 carriers of the T-allele in Europeans [1,2], primarily because of elevations in appetite and energy intake [3,4]
No statistical differences in baseline (−1.5 h) and pre-meal (0 h) concentrations were shown for TG (p ≥ 0.293; effect sizes (ES) ≤ 0.44), non-esterified fatty acid (NEFA) (p ≥ 0.695; ES ≤ 0.16), glucose (p ≥ 0.472; ES ≤ 0.30), and insulin (p ≥ 0.501; ES ≤ 0.28) between AAs and TTs
The present study indicates that postprandial concentrations of TG, NEFA, glucose, and insulin were similar in a male cohort of FTO rs9939609 AAs and TTs

Summary

Introduction

At the fat-mass and obesity-associated gene (FTO) rs9939609 single nucleotide polymorphism (SNP), carriers of the obesity-risk A-allele present a higher risk of obesity compared to homozygousNutrients 2020, 12, 3857; doi:10.3390/nu12123857 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 3857 carriers of the T-allele in Europeans [1,2], primarily because of elevations in appetite and energy intake [3,4]. Further work reports an increased propensity for cardiovascular disease (CVD) in carriers of the FTO rs9939609 A-allele [5,6]. A-allele had lower high-density lipoprotein cholesterol (HDL) and higher random triacylglycerol (TG) concentrations than non-carriers, indicating that the FTO-CVD relationship may be explained by differences in blood lipids [7]. Others have shown no influence of the FTO A-allele on fasting blood lipid profiles [8]. These conflicting findings potentially imply that any FTO-related variations in blood lipids and other CVD risk markers, such as glucose and insulin, may be mediated by the influence of the FTO gene on weight [8]. To help determine if weight management strategies are warranted, experiments that carefully control for weight and other characteristics are needed to elucidate the influence of the FTO per se on blood lipid concentrations

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