MiR-193b-365, a brown fat enriched microRNA cluster, is essential for brown fat differentiation

• Main Authors: Sun, Lei (Contributor), Xie, Huangming (Author), Mori, Marcelo A. (Author), Alexander, Ryan (Author), Yuan, Bingbing B. (Contributor), Hattangadi, Shilpa M. (Author), Liu, Qingqing (Author), Kahn, C. Ronald (Author), Lodish, Harvey F (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Lodish, Harvey F. (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2012-10-22T15:29:36Z.
• Subjects: Article
• Online Access: Get fulltext

2012 February 1
Mammals have two principal types of fat. White adipose tissue primarily serves to store extra energy as triglycerides, whereas brown adipose tissue is specialized to burn lipids for heat generation and energy expenditure as a defence against cold and obesity1, 2. Recent studies have demonstrated that brown adipocytes arise in vivo from a Myf5-positive, myoblastic progenitor by the action of Prdm16 (PR domain containing 16). Here, we identified a brown-fat-enriched miRNA cluster, MiR-193b-365, as a key regulator of brown fat development. Blocking miR-193b and/or miR-365 in primary brown preadipocytes markedly impaired brown adipocyte adipogenesis by enhancing Runx1t1 (runt-related transcription factor 1; translocated to, 1) expression, whereas myogenic markers were significantly induced. Forced expression of Mir193b and/or Mir365 in C2C12 myoblasts blocked the entire programme of myogenesis, and, in adipogenic conditions, miR-193b induced myoblasts to differentiate into brown adipocytes. Mir193b-365 was upregulated by Prdm16 partially through Pparα. Our results demonstrate that Mir193b-365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis.
National Institutes of Health (U.S.) (Grant DK047618)
National Institutes of Health (U.S.) (Grant DK 068348)
National Institutes of Health (U.S.) (Grant DK076848)
Natioanl Institutes of Health (U.S.) (Grant 5P01 HL066105)
Singapore-MIT Alliance (Grant C-382-641-001-091)
Singapore-MIT Alliance (Graduate Fellowship)