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

• Autores: Hung, Chien Min; Martinez Calejman, Camila; Sanchez Gurmaches, Joan; Li, Huawei; Clish, Clary B.; Hettmer, Simone; Wagers, Amy J.; Guertin, David A.
• Año de publicación: 2014
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: BROWN FAT; MTORC2; THERMOGENESIS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The invivo 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 invivo 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 invitro 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.
Fil: Hung, Chien Min. University Of Massachussets. Medical School; Estados Unidos
Fil: Martinez Calejman, Camila. University Of Massachussets. Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Huawei. University Of Massachussets. Medical School; Estados Unidos
Fil: Clish, Clary B.. Massachusetts Institute of Technology; Estados Unidos
Fil: Hettmer, Simone. Harvard University. Harvard School of Public Health; Estados Unidos. Howard Hughes Medical Institute; Estados Unidos. Dana Farber Cancer Institute; . Children’s Hospital; Estados Unidos. One Joslin Place; Estados Unidos
Fil: Wagers, Amy J.. Harvard University. Harvard School of Public Health; Estados Unidos. Dana Farber Cancer Institute; . Howard Hughes Medical Institute; Estados Unidos. One Joslin Place; Estados Unidos
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos