Novel Genetic Locus of Visceral Fat and Systemic Inflammation

J Clin Endocrinol Metab. 2019 Sep 1;104(9):3735-3742. doi: 10.1210/jc.2018-02656.

Abstract

Context: Visceral fat (VF), more than fat elsewhere in the body [mostly subcutaneous fat (SF)], promotes systemic inflammation and related disease. The mechanisms of preferentially visceral accumulation of body fat are largely unknown.

Objective: To identify genetic loci and mechanistic pathways of preferential accumulation of VF and associated low-grade systemic inflammation.

Design: Genome-wide association study (GWAS).

Setting and participants: Population-based cohort of 1586 adolescents (aged 12 to 19 years) and adults (aged 36 to 65 years).

Main outcome measures: Abdominal VF and SF were measured with MRI, total body fat (TBF) was assessed with bioimpedance, and low-grade systemic inflammation was examined by serum C-reactive protein (CRP) measurement.

Results: This GWAS of preferential accumulation of VF identified a significant locus on chromosome 6 at rs803522 (P = 1.1 × 10-9 or 4.3 × 10-10 for VF adjusted for SF or TBF, respectively). The major allele was associated with more VF; the association was similar in adolescents and adults. The allele was also associated with higher CRP level, but this association was stronger in adults than adolescents (P for interaction = 4.5 × 10-3). In adults, VF was a significant mediator (P = 1.9× 10-4) in the association between the locus and CRP, explaining 30% of the mediation. The locus was near ATG5, encoding an autophagy molecule reported to modulate adipocyte size and macrophage polarization.

Conclusion: A genetic locus near ATG5 regulates preferential accumulation of VF (vs SF) in youth and adulthood and contributes to the development of systemic inflammation in adulthood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis*
  • Body Mass Index
  • Child
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Loci*
  • Genome-Wide Association Study*
  • Humans
  • Inflammation / genetics*
  • Inflammation / pathology
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Subcutaneous Fat / metabolism*
  • Young Adult

Substances

  • Biomarkers