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Cell Rep DOI:10.1016/j.celrep.2014.06.007

Rictor/mTORC2 loss in the Myf5 lineage reprograms brown fat metabolism and protects mice against obesity and metabolic disease.

Publication TypeJournal Article
Year of Publication2014
AuthorsHung, C-M, Calejman, CMartinez, Sanchez-Gurmaches, J, Li, H, Clish, CB, Hettmer, S, Wagers, AJ, Guertin, DA
JournalCell Rep
Date Published2014 Jul 10
KeywordsAdipocytes, Brown, Adipogenesis, Animals, Bone Morphogenetic Protein 7, Carrier Proteins, Cell Lineage, Cells, Cultured, Energy Metabolism, Mice, Multiprotein Complexes, Muscle, Skeletal, Myogenic Regulatory Factor 5, Obesity, Proto-Oncogene Proteins c-akt, Signal Transduction, Thermogenesis, TOR Serine-Threonine Kinases

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.


Alternate JournalCell Rep
PubMed ID25001283
PubMed Central IDPMC4096327
Grant ListR00CA129613 / CA / NCI NIH HHS / United States
R01 DK094004 / DK / NIDDK NIH HHS / United States
R00 CA129613 / CA / NCI NIH HHS / United States
R01DK094004 / DK / NIDDK NIH HHS / United States
T32 HG000035 / HG / NHGRI NIH HHS / United States
DK09300 / DK / NIDDK NIH HHS / United States
/ / Howard Hughes Medical Institute / United States