eScholarship@UMMS

Title

Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease

Authors

Chien-Min Hung, University of Massachusetts Medical SchoolFollow
Camila Martinez Calejman, University of Massachusetts Medical SchoolFollow
Joan Sanchez-Gurmaches, University of Massachusetts Medical SchoolFollow
Huawei Li, University of Massachusetts Medical SchoolFollow
Clary B. Clish, Broad Institute
Simone Hettmer, Harvard Stem Cell Institute
Amy J. Wagers, Harvard Stem Cell Institute
David A. Guertin, University of Massachusetts Medical SchoolFollow

Student Author(s)

Chien-Min Hung

GSBS Program

Interdisciplinary Graduate Program

UMMS Affiliation

Program in Molecular Medicine

Date

7-4-2014

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.

Comments

Citation: 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

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/).

Related Resources

Link to article in PubMed

Journal Title

Cell Reports

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