DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity
Laplante, Mathieu ...
DEP domain-containig mTOR-interacting protein (DEPTOR) inhibits the mechanistic target of rapamty-cin (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 inadipogenesis. 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 ofobesity. We show that DEPTOR is induced by glucocrtioids during adipogenesisand that its overexpression promotes, while its suppression blocks, adipogenesis. DEPTOR activates the proadipogenic Akt/PKB-PRAR-[ni] axisby dampening mTORC1-mediated feedback inhibition of insulin signaling. These results establish DEPTOR as a new regulator of adipogenesis.
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