Impact of Variation Near MC4R on Whole-body Fat Distribution, Liver Fat, and Weight Loss

Authors

  • Axel Haupt,

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Claus Thamer,

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Martin Heni,

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Otto Tschritter,

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Jürgen Machann,

    1. Section on Experimental Radiology, Department of Diagnostic Radiology, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Fritz Schick,

    1. Section on Experimental Radiology, Department of Diagnostic Radiology, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Fausto Machicao,

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Hans-Ulrich Häring,

    Corresponding author
    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
      (Hans-Ulrich.Haering@med.uni-tuebingen.de)
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  • Harald Staiger,

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
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  • Andreas Fritsche

    1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
    2. Nutritional and Preventive Medicine, Department of Internal Medicine, Eberhard-Karls-University Tübingen, Tübingen, Germany
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(Hans-Ulrich.Haering@med.uni-tuebingen.de)

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 ≥ 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 ≥ 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.

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