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Publication
Rictor/mTORC2 loss in the Myf5 lineage reprograms brown fat metabolism and
protects mice against obesity and metabolic disease.
Authors Hung CM, Calejman CM, Sanchez-Gurmaches J, Li H, Clish CB, Hettmer S, Wagers AJ,
Guertin DA
Submitted By Submitted Externally on 7/30/2018
Status Published
Journal Cell reports
Year 2014
Date Published 7/10/2014
Volume : Pages 8 : 256 - 71
PubMed Reference 25001283
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.






Genes
SymbolDescription
Akt1thymoma viral proto-oncogene 1

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