MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade

Authors

  • Jiyun Ahn,

    1. Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea
    2. Division of Food Biotechnology, University of Science and Technology, Daejeon, Korea
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  • Hyunjung Lee,

    1. Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea
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  • Chang Hwa Jung,

    1. Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea
    2. Division of Food Biotechnology, University of Science and Technology, Daejeon, Korea
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  • Tae Il Jeon,

    1. Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea
    2. Division of Animal Science, University of Chonnam National University, Gwangju, Korea
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  • Tae Youl Ha

    Corresponding author
    1. Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea
    2. Division of Food Biotechnology, University of Science and Technology, Daejeon, Korea
    • Corresponding author: Tel: +82 31 780 9054 Fax: +82 31 780 9225;

      E-mail: tyhap@kfri.re.kr

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Abstract

Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR-146b expression was markedly increased during adipogenesis in 3T3-L1 cells. Differentiation of 3T3-L1 was induced by overexpression of miR-146b. Conversely, inhibition of miR-146b decreased adipocyte differentiation. Bioinformatics-based studies suggested that SIRT1 is a target of miR-146b. Further analysis confirmed that SIRT1 was negatively regulated by miR-146b. We also observed that miR-146b bound directly to the 3′-untranslated region of SIRT1 and inhibited adipogenesis through SIRT1 downregulation. The miR-146b/SIRT1 axis mediates adipogenesis through increased acetylation of forkhead box O1 (FOXO1). Expression of miR-146b was increased and SIRT1 mRNA subsequently decreased in the adipose tissues of diet-induced and genetically obese mice. Furthermore, in vivo knockdown of miR-146b by a locked nucleic acid miR-146b antagomir significantly reduced body weight and fat volume in accordance with upregulation of SIRT1 and subsequent acetylation of FOXO1. Therefore, the miR-146b/SIRT1 pathway could be a potential target for obesity prevention and treatment.

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