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

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

    119 Citationer (Scopus)

    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.

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

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