GSBS Student Publications
GSBS Program
Interdisciplinary Graduate Program
Publication Date
2014-07-04
UMMS Affiliation
Program in Molecular Medicine
Document Type
Article
Disciplines
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology
Abstract
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.
Rights and Permissions
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/).
DOI of Published Version
10.1016/j.celrep.2014.06.007
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
Journal/Book/Conference Title
Cell Reports
Related Resources
PubMed ID
25001283
Repository Citation
Hung, Chien-Min; Calejman, Camila Martinez; Sanchez-Gurmaches, Joan; Li, Huawei; Clish, Clary B.; Hettmer, Simone; Wagers, Amy J.; and Guertin, David A., "Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease" (2014). GSBS Student Publications. 1859.
https://escholarship.umassmed.edu/gsbs_sp/1859
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons