MicroRNA-196 Regulates HOX Gene Expression in Human Gluteal Adipose Tissue.

Abstract

ObjectiveLower body fat is associated with diminishing cardiometabolic risk. Physiological differences between gluteofemoral and abdominal subcutaneous adipocyte functions are known, but the molecular basis for depot differences in adipocyte function is poorly understood. Our objective is to identify depot-differences in microRNA expression in human abdominal and gluteofemoral subcutaneous adipose tissues and their implication in gene regulation.MethodsAbdominal and gluteofemoral adipose tissue aspirates obtained from 18 participants (9M/9F, age 30±1.5 years, BMI 27.3.±1.23 kg/m2) analyzed for miRNA expression profiles by next-generation DNA sequencing. The raw reads were mapped to miRBase v17 and differentially expressed miRNAs were confirmed by qRT-PCR. The hsa-mimic-miR196a was transfected into cultured abdominal preadipocytes isolated from 5 obese women. Target gene expression was evaluated by RT-qPCR.ResultsAmong the 640 miRNAs detected in adipose tissue; miR196a2, miR196a1, miR196b and miR204 showed a higher expression in gluteofemoral (fold change=2.7, 2.3, 1.7 and 2.3 respectively) independent of the sex. Bioinformatic analyses and human primary preadipocyte transfection with miR196 suggested that the differentially expressed miRNAs could modulate directly or indirectly Homeobox (HOX) genes expression.ConclusionMiR196 gene family could play an important role in the regulation of HOX gene expression in subcutaneous AT and then in fat distribution variation.