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

Research output: Contribution to journalJournal articleResearchpeer-review


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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.

Original languageEnglish
JournalCell Death and Differentiation
Issue number6
Pages (from-to)1003-12
Number of pages10
Publication statusPublished - Jun 2012

    Research areas

  • 3' Untranslated Regions, Adipose Tissue, Adult, Animals, Animals, Newborn, Base Sequence, Cell Differentiation, Diabetes Mellitus, Type 2, Diet, Disease Models, Animal, Down-Regulation, Female, Growth Differentiation Factor 3, HEK293 Cells, Humans, Lipid Metabolism, Male, MicroRNAs, RNA Interference, RNA, Small Interfering, Rats, Rats, Wistar, Journal Article, Research Support, Non-U.S. Gov't

ID: 51555070