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Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • D Ferland-McCollough
  • Denise S Fernandez-Twinn
  • I G Cannell
  • H David
  • M Warner
  • A A Vaag
  • J Bork-Jensen
  • C Brøns
  • T W Gant
  • A E Willis
  • K Siddle
  • M Bushell
  • Susan E Ozanne
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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.

OriginalsprogEngelsk
TidsskriftCell Death and Differentiation
Vol/bind19
Udgave nummer6
Sider (fra-til)1003-12
Antal sider10
ISSN1350-9047
DOI
StatusUdgivet - jun. 2012

ID: 51555070