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Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits
glucose uptake in adipocytes
#MMPMID25422441
Mullins GR
; Wang L
; Raje V
; Sherwood SG
; Grande RC
; Boroda S
; Eaton JM
; Blancquaert S
; Roger PP
; Leitinger N
; Harris TE
Proc Natl Acad Sci U S A
2014[Dec]; 111
(49
): 17450-5
PMID25422441
show ga
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 ?-adrenergic receptor inhibits insulin-stimulated glucose uptake in
adipocytes, the mechanism has remained unclear. Here we report that
?-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.
|3T3-L1 Cells
[MESH]
|Adipocytes/*cytology
[MESH]
|Animals
[MESH]
|Catecholamines/*chemistry
[MESH]
|Cyclic AMP-Dependent Protein Kinases/metabolism
[MESH]
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