Expression data from mouse primary brown preadipocytes. Mus musculus

Brown adipocytes are specialized for heat generation and energy expenditure as a defense against cold and obesity. Recent studies demonstrate that brown adipocytes arise in vivo from a Myf5-positive, myoblastic progenitor by the action of PRDM16. 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 dramatically impaired brown adipocyte adipogenesis whereas myogenic markers were significantly induced. Forced expression of miR-193b and/or miR-365 in C2C12 myoblasts blocked the entire program of myogenesis, and miR-193b induced myoblasts to differentiate into brown adipocytes. Mir-193b-365 was upregulated by PRDM16. Our results demonstrate that mir-193b-365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis. Overall design: To study if miR-193b-365 is required for brown adipocyte adipogenesis, mRNAs from cultured primary brown adipocytes (Day 4) transfected with each locked nucleic acid (LNA) miRNA inhibitor or Control inhibitor were analyzed by microarray analysis.