Brown adipose tissue (BAT) represents a promising agent to ameliorate obesity and other metabolic disorders. However, the abundance of BAT decreases with age and BAT paucity is a common feature of obese subjects. As brown adipocytes and myoblasts share a common Myf5 lineage origin, elucidating the molecular mechanisms underlying the fate choices of brown adipocytes versus myoblasts may lead to novel approaches to expand BAT mass. Here we identify MyoD as a key negative regulator of brown adipocyte development. CRISPR/CAS9-mediated deletion of MyoD in C2C12 myoblasts facilitates their adipogenic transdifferentiation. MyoD knockout downregulates miR-133 and upregulates the miR-133 target Igf1r, leading to amplification of PI3K-Akt signaling. Accordingly, inhibition of PI3K or Akt abolishes the adipogenic gene expression of MyoD null myoblasts. Strikingly, loss of MyoD converts satellite cell-derived primary myoblasts to brown adipocytes through upregulation of Prdm16, a target of miR-133 and key determinant of brown adipocyte fate. Conversely, forced expression of MyoD in brown preadipocytes blocks brown adipogenesis and upregulates the expression of myogenic genes. Importantly, miR-133a knockout significantly blunts the inhibitory effect of MyoD on brown adipogenesis. Our results establish MyoD as a negative regulator of brown adipocyte development by upregulating miR-133 to suppress Akt signaling and Prdm16.
Pubmed ID: 28117277 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsCell line HEK293-A is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsMus musculus with name FVB.Cg-Myod1tm2.1(icre)Glh/J from IMSR.
View all literature mentionsMus musculus with name C57BL/10ScSn-Dmdmdx/J from IMSR.
View all literature mentions