Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes

GR Mullins, L Wang, V Raje… - Proceedings of the …, 2014 - National Acad Sciences
GR Mullins, L Wang, V Raje, SG Sherwood, RC Grande, S Boroda, JM Eaton, S Blancquaert…
Proceedings of the National Academy of Sciences, 2014National Acad Sciences
Anabolic and catabolic signaling oppose one another in adipose tissue to maintain cellular
and organismal homeostasis, but these pathways are often dysregulated in metabolic
disorders. Although it has long been established that stimulation of the β-adrenergic
receptor inhibits insulin-stimulated glucose uptake in adipocytes, the mechanism has
remained unclear. Here we report that β-adrenergic–mediated inhibition of glucose uptake
requires lipolysis. We also show that lipolysis suppresses glucose uptake by inhibiting the …
Anabolic and catabolic signaling oppose one another in adipose tissue to maintain cellular and organismal homeostasis, but these pathways are often dysregulated in metabolic disorders. Although it has long been established that stimulation of the β-adrenergic receptor inhibits insulin-stimulated glucose uptake in adipocytes, the mechanism has remained unclear. Here we report that β-adrenergic–mediated inhibition of glucose uptake requires lipolysis. We also show that lipolysis suppresses glucose uptake by inhibiting the mammalian target of rapamycin (mTOR) complexes 1 and 2 through complex dissociation. In addition, we show that products of lipolysis inhibit mTOR through complex dissociation in vitro. These findings reveal a previously unrecognized intracellular signaling mechanism whereby lipolysis blocks the phosphoinositide 3-kinase–Akt–mTOR pathway, resulting in decreased glucose uptake. This previously unidentified mechanism of mTOR regulation likely contributes to the development of insulin resistance.
National Acad Sciences