Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes.

Abstract

Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease.This work was funded by the BBSRC (project grants BB/F-15364/1 and BB/F-14279/1). SEO is a British Heart Foundation Senior Fellow (FS/09/029/27902), MB is an MRC Senior Fellow and AEW is a BBSRC Professorial Fellow. KS and SEO are members of the MRC Centre for Obesity and Related Metabolic Diseases (MRC-CORD), which also provided a studentship for MW. KS is a member of the European Union COST Action BM0602