MicroRNAs Induced During Adipogenesis that Accelerate Fat Cell Development Are Downregulated in Obesity

  1. Huangming Xie1,2,3,
  2. Bing Lim2,3,4 and
  3. Harvey F. Lodish1,2,5
  1. 1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts;
  2. 2Computation and Systems Biology, Singapore-MIT Alliance, National University of Singapore, Singapore;
  3. 3Stem Cell and Developmental Biology, Genome Institute of Singapore, A*STAR (Agency for Science, Technology and Research), Singapore;
  4. 4Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and
  5. 5Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  1. Corresponding author: Bing Lim, limb1{at}gis.a-star.edu.sg, or Harvey F. Lodish, lodish{at}wi.mit.edu.

Abstract

OBJECTIVE We investigated the regulation and involvement of microRNAs (miRNAs) in fat cell development and obesity.

RESEARCH DESIGN AND METHODS Using miRNA microarrays, we profiled the expression of >370 miRNAs during adipogenesis of preadipocyte 3T3-L1 cells and adipocytes from leptin deficient ob/ob and diet-induced obese mice. Changes in key miRNAs were validated by RT-PCR. We further assessed the contribution of the chronic inflammatory environment in obese adipose tissue to the dysregulated miRNA expression by tumor necrosis factor (TNF)-α treatment of adipocytes. We functionally characterized two adipocyte-enriched miRNAs, miR-103 and miR-143, by a gain-of-function approach.

RESULTS Similar miRNAs were differentially regulated during in vitro and in vivo adipogenesis. Importantly, miRNAs that were induced during adipogenesis were downregulated in adipocytes from both types of obese mice and vice versa. These changes are likely associated with the chronic inflammatory environment, since they were mimicked by TNF-α treatment of differentiated adipocytes. Ectopic expression of miR-103 or miR-143 in preadipocytes accelerated adipogenesis, as measured both by the upregulation of many adipogenesis markers and by an increase in triglyceride accumulation at an early stage of adipogenesis.

CONCLUSIONS Our results provide the first experimental evidence for miR-103 function in adipose biology. The remarkable inverse regulatory pattern for many miRNAs during adipogenesis and obesity has important implications for understanding adipose tissue dysfunction in obese mice and humans and the link between chronic inflammation and obesity with insulin resistance.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received September 21, 2008.
    • Accepted January 25, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes vol. 58 no. 5 1050-1057
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