title: Inhibition of in vitro and in vivo brown fat differentiation program by myostatin.
abstract: OBJECTIVE
  Obesity arises mainly due to the imbalance between energy storage and its expenditure. Metabolically active brown adipose tissue (BAT) has recently been detected in humans and has been proposed as a new target for anti-obesity therapy because of its unique capacity to regulate energy expenditure. Myostatin (Mst), a negative regulator of muscle mass, has been identified as a potential target to regulate overall body composition. Although the beneficial effects of Mst inhibition on muscle mass are well known, its role in the regulation of lipid metabolism, and energy expenditure is not very clear.
  
  
  METHODS
  We tested the effects of Mst inhibition on the gene regulatory networks that control BAT differentiation using both in vivo and in vitro model systems. PRDM16 and UCP1, two key regulators of brown fat differentiation were significantly up regulated in levator-ani (LA) and gastrocnemius (Gastroc) muscles as well as in epididymal (Epi) and subcutaneous (SC) fat pads isolated from Mst knock out (Mst KO) male mice compared with wild type (WT) mice.
  
  
  RESULTS
  Using mouse embryonic fibroblast (MEFs) primary cultures obtained from Mst KO group compared to the WT group undergoing adipogenic differentiation, we also demonstrate a significant increase in select genes and proteins that improve lipid metabolism and energy expenditure.
  
  
  CONCLUSIONS
  Treatment of Mst KO MEFs with recombinant Mst protein significantly inhibited the gene expression levels of UCP1, PRDM16, PGC1-α/β as well as BMP7. Future studies to extend these findings and explore the therapeutic potential of Mst inhibition on metabolic disorders are warranted.
authors.affiliation: Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Braga
authors.forename: Shehla
authors.initials: S
authors.lastname: Pervin
authors.forename: Keith
authors.initials: K
authors.lastname: Norris
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Rajan
authors.initials: R
authors.lastname: Singh
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D053263:Gene Regulatory Networks; D005838:Genotype; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal; D055435:Myostatin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D055419:Bone Morphogenetic Protein 7; D004268:DNA-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C525912:Mstn protein, mouse; D055435:Myostatin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C521133:Prdm16 protein, mouse; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C525820:bmp7 protein, mouse