MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition.

Abstract:

BACKGROUND:Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. METHODS:An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdominal subcutaneous adipose tissue. FINDINGS:We found that rs11614913, a SNP within pre-miR-196a-2 at the HOXC locus, is an eQTL for miR-196a expression in abdominal subcutaneous adipose tissue (ASAT). Observations in large cohorts showed that rs11614913 increased waist-to-hip ratio, which was driven specifically by an expansion in ASAT. In further experiments, rs11614913 was associated with adipocyte size. Functional studies and transcriptomic profiling of miR-196a knock-down pre-adipocytes revealed a role for miR-196a in regulating pre-adipocyte proliferation and extracellular matrix pathways. INTERPRETATION:These data identify a role for miR-196a in regulating human body fat distribution. FUND: This work was supported by the Medical Research Council and Novo Nordisk UK Research Foundation (G1001959) and Swedish Research Council. We acknowledge the OBB-NIHR Oxford Biomedical Research Centre and the British Heart Foundation (BHF) (RG/17/1/32663). Work performed at the MRC Epidemiology Unit was funded by the United Kingdom's Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Hilton C,Neville MJ,Wittemans LBL,Todorcevic M,Pinnick KE,Pulit SL,Luan J,Kulyté A,Dahlman I,Wareham NJ,Lotta LA,Arner P,Lindgren CM,Langenberg C,Karpe F

doi

10.1016/j.ebiom.2019.05.047

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

467-475

issn

2352-3964

pii

S2352-3964(19)30355-X

journal_volume

44

pub_type

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