DEPTOR Cell-Autonomously Promotes Adipogenesis, and Its Expression Is Associated with Obesity

Author(s)

Laplante‚ M. ; Horvat‚ S. ; Festuccia‚ W.T. ; Birsoy‚ K. ; Prevorsek‚ Z. ; Efeyan‚ A. ; Sabatini‚ D.M.

• Document type: Journal article
• Source: Cell Metabolism; v. 16, n. 2, p. 202-212, 2012.
• Web of Science Citations: 62

Abstract

DEP domain-containing mTOR-interacting protein (DEPTOR) inhibits the mechanistic target of rapamycin (mTOR), but its in vivo functions are unknown. Previous work indicates that Deptor is part of the Fob3a quantitative trait locus (QTL) linked to obesity/leanness in mice, with Deptor expression being elevated in white adipose tissue (WAT) of obese animals. This relation is unexpected, considering the positive role of mTOR in adipogenesis. Here, we dissected the Fob3a QTL and show that Deptor is the highest-priority candidate promoting WAT expansion in this model. Consistently, transgenic mice overexpressing DEPTOR accumulate more WAT. Furthermore, in humans, DEPTOR expression in WAT correlates with the degree of obesity. We show that DEPTOR is induced by glucocorticoids during adipogenesis and that its overexpression promotes, while its suppression blocks, adipogenesis. DEPTOR activates the proadipogenic Akt/PKB-PPAR-gamma axis by dampening mTORC1-mediated feedback inhibition of insulin signaling. These results establish DEPTOR as a new regulator of adipogenesis. (AU)

• FAPESP's process: 10/10909-8 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 09/15354-7 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Grants - Young Investigators Grants