Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Authors
Hung, Chien-MinCalejman, Camila Martinez
Sanchez-Gurmaches, Joan
Li, Huawei
Clish, Clary B.
Hettmer, Simone
Wagers, Amy J.
Guertin, David A.
Student Authors
Chien-Min HungUMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2014-07-04
Metadata
Show full item recordAbstract
The in vivo functions of mechanistic target of rapamycin complex 2 (mTORC2) and the signaling mechanisms that control brown adipose tissue (BAT) fuel utilization and activity are not well understood. Here, by conditionally deleting Rictor in the Myf5 lineage, we provide in vivo evidence that mTORC2 is dispensable for skeletal muscle development and regeneration but essential for BAT growth. Furthermore, deleting Rictor in Myf5 precursors shifts BAT metabolism to a more oxidative and less lipogenic state and protects mice from obesity and metabolic disease at thermoneutrality. We additionally find that Rictor is required for brown adipocyte differentiation in vitro and that the mechanism specifically requires AKT1 hydrophobic motif phosphorylation but is independent of pan-AKT signaling and is rescued with BMP7. Our findings provide insights into the signaling circuitry that regulates brown adipocytes and could have important implications for developing therapies aimed at increasing energy expenditure as a means to combat human obesity.Source
Hung CM, Calejman CM, Sanchez-Gurmaches J, Li H, Clish CB, Hettmer S, Wagers AJ, Guertin DA. Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease. Cell Rep. 2014 Jul 10; 8(1):256-271. doi: 10.1016/j.celrep.2014.06.007. Link to article on publisher's site
DOI
10.1016/j.celrep.2014.06.007Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33332PubMed ID
25001283Related Resources
Link to article in PubMedRights
Copyright 2014 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2014.06.007