Format

Send to

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

Novel Genetic Locus of Visceral Fat and Systemic Inflammation.

Shin J1,2,3, Syme C1,2,3, Wang D1,2,3, Richer L4, Pike GB5, Gaudet D6, Paus T7,8, Pausova Z1,2,3.

Author information

1
The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
2
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
3
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
4
Department of Health Sciences, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
5
Department of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
6
Lipidology Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, Saguenay, Quebec, Canada.
7
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
8
Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.

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.

PMID:
30942860
PMCID:
PMC6642667
[Available on 2020-04-03]
DOI:
10.1210/jc.2018-02656

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center