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Cell Death Differ. 2012 Jun;19(6):1003-12. doi: 10.1038/cdd.2011.183. Epub 2012 Jan 6.

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

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1
MRC Toxicology Unit, Lancaster Road, Leicester LE1 9HN, UK.

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.

PMID:
22223106
PMCID:
PMC3354052
DOI:
10.1038/cdd.2011.183
[Indexed for MEDLINE]
Free PMC Article
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