期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 234, 期 4, 页码 3800-3813出版社
WILEY
DOI: 10.1002/jcp.27148
关键词
adipocytes; browning; microRNA-133a; PR domain containing 16; reversine; uncoupling protein 1
资金
- National Research Foundation of Korea [2012R1A5A2A28671860, 2017R1A2B3002186, 2017R1A6A3A04001986]
- Ministry of Science, ICT & Future Planning
- National Research Foundation of Korea [2017R1A2B3002186, 2012R1A5A2A28671860, 2017R1A6A3A04001986] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Brown adipocytes are characterized by a high number of uncoupling protein 1 (UCP1)-positive mitochondrial content and increased thermogenic capacity. As UCP1-enriched cells can consume lipids by generating heat, browning of white adipocytes is now highlighted as a promising approach for the prevention of obesity and obesity-associated metabolic diseases. Upon cold exposure or -adrenergic stimuli, downregulation of microRNA-133 (miR-133) elevates the expression levels of PR domain containing 16 (Prdm16), which has been shown to be a brown adipose determination factor, in brown adipose tissue and subcutaneous white adipose tissues (WAT). Here, we show that treatment of reversine to white adipocytes induces browning via suppression of miR-133a. Reversine treatment promoted the expression of brown adipocyte marker genes, such as Prdm16 and UCP1, increasing the mitochondrial content, while decreasing the levels of miR-133a and white adipocyte marker genes. Ectopic expression of miR-133a mimic reversed the browning effects of the reversine treatment. Moreover, intraperitoneal administration of reversine in mice upregulated thermogenesis and resulted in resistance to high-fat diet-mediated weight gain as well as browning of subcutaneous and epididymal WAT. Taken together, we found a novel way to promote browning of white adipocytes through downregulation of miR-133a followed by activation of Prdm16, with a synthetic chemical, reversine.
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