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

Ferland-McCollough, D. et al. (2012) Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death and Differentiation, 19(6), pp. 1003-1012. (doi: 10.1038/cdd.2011.183) (PMID:22223106) (PMCID:PMC3354052)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Ferland-McCollough, D., Fernandez-Twinn, D.S., Cannell, I.G., David, H., Warner, M., Vaag, A.A., Bork-Jensen, J., Brøns, C., Gant, T.W., Willis, A.E., Siddle, K., Bushell, M., and Ozanne, S.E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Death and Differentiation
Publisher:Nature Publishing Group
ISSN (Online):1476-5403
Published Online:06 January 2012
Copyright Holders:Copyright © 2012 Macmillan Publishers Limited
First Published:First published in Cell Death and Differentiation 19(6): 1003-1012
Publisher Policy:Reproduced under a Creative Commons License

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