Disclosure: The authors declare no conflict of interest.
Inhibition of in vitro and in vivo brown fat differentiation program by myostatin
Article first published online: 19 JUL 2013
Copyright © 2012 The Obesity Society
Volume 21, Issue 6, pages 1180–1188, June 2013
How to Cite
Braga, M., Pervin, S., Norris, K., Bhasin, S. and Singh, R. (2013), Inhibition of in vitro and in vivo brown fat differentiation program by myostatin. Obesity, 21: 1180–1188. doi: 10.1002/oby.20117
- Issue published online: 26 JUL 2013
- Article first published online: 19 JUL 2013
- Accepted manuscript online: 5 NOV 2012 05:52PM EST
- Manuscript Accepted: 21 SEP 2012
- Manuscript Received: 19 MAR 2012
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.
Design and 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.
Conclusion: 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.