title: Impact of variation near MC4R on whole-body fat distribution, liver fat, and weight loss.
abstract: Polymorphisms near the melanocortin-4 receptor (MC4R) gene locus are associated with body weight. Recent studies have shown that they influence insulin sensitivity and incidence of the metabolic syndrome. Thus, we hypothesized that the candidate single-nucleotide polymorphism (SNP) rs17782313 near MC4R additionally influences body fat distribution and its change during lifestyle intervention. To test this, 343 German subjects were genotyped for SNP rs17782313. Body composition was assessed using magnetic resonance technique. Subjects were characterized by an oral glucose tolerance test (OGTT). A subgroup of 242 subjects participated in a 9-month lifestyle intervention. In the overall cohort, the C allele was associated with a higher BMI (P=0.0013), but had no impact on glucose tolerance or insulin sensitivity (all P>or=0.10). There was an effect of the SNP on total body fat (P=0.022) and nonvisceral fat (P=0.017), but not on liver fat and visceral fat (all P>or=0.33). In the subgroup undergoing lifestyle intervention, SNP rs17782313 had no impact on changes in body weight or fat distribution. Despite an association with BMI and nonvisceral adipose tissue, the SNP rs17782313 did not influence visceral adipose tissue. Thus, this candidate SNP for human obesity may preferentially affect the accumulation of subcutaneous adipose tissue. Furthermore, the variation near MC4R has no effect on success of weight loss during lifestyle intervention.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haupt
authors.forename: Claus
authors.initials: C
authors.lastname: Thamer
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.forename: Otto
authors.initials: O
authors.lastname: Tschritter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000328:Adult; D050218:Body Fat Distribution; D001835:Body Weight / Q000235:genetics*; D003430:Cross-Sectional Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics*
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D004247:DNA