The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

Abstract

The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the MC4R gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance.

The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis

“…However, there are many inconsistencies and contradictions in the published data on these two polymorphic sites and metabolic abnormalities. Some researchers reported that C allele of the rs17782313 polymorphism is correlated with a higher level of body mass index (BMI) ( 38 – 43 ), waist circumference (WC) ( 40 , 44 ), waist-to-hip ratio (WHR) ( 23 ), glucose (GLU) ( 16 – 18 ), insulin (INS) ( 14 ), triglyceride (TG) ( 19 – 21 ), total cholesterol (TC) ( 21 ) or low-density lipoprotein cholesterol (LDL-C) ( 21 ), and a lower level of high-density lipoprotein cholesterol (HDL-C) ( 45 ), while the experimental data obtained by other investigators could not support these conclusions ( 46 – 53 ). There were also lots of disagreements on the relations between the PGC1α rs8192678 variant and the indexes of obesity, glucometabolic disorder and dyslipidemia.…”