Glucose uptake in brown fat cells is dependent on mTOR complex 2-promoted GLUT1 translocation.
Brown adipose tissue is the primary site for thermogenesis and can consume, in addition to free fatty acids, a very high amount of glucose from the blood, which can both acutely and chronically affect glucose homeostasis. Here, we show that mechanistic target of rapamycin (mTOR) complex 2 has a novel role in β3-adrenoceptor-stimulated glucose uptake in brown adipose tissue. We show that β3-adrenoceptors stimulate glucose uptake in brown adipose tissue via a signaling pathway that is comprised of two different parts: one part dependent on cAMP-mediated increases in GLUT1 transcription and de novo synthesis of GLUT1 and another part dependent on mTOR complex 2-stimulated translocation of newly synthesized GLUT1 to the plasma membrane, leading to increased glucose uptake. Both parts are essential for β3-adrenoceptor-stimulated glucose uptake. Importantly, the effect of β3-adrenoceptor on mTOR complex 2 is independent of the classical insulin-phosphoinositide 3-kinase-Akt pathway, highlighting a novel mechanism of mTOR complex 2 activation.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE -0691 Stockholm, Sweden.
Jessica M
JM
Olsen
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE -0691 Stockholm, Sweden Department of Pharmacology and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia Department of Pharmacology and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia.
Masaaki
M
Sato
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE -0691 Stockholm, Sweden Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Olof S
OS
Dallner
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE -0691 Stockholm, Sweden.
Anna L
AL
Sandström
Institute of Biology Valrose, Centre National de la Recherche Scientifique UMR 7277, Institut National de la Santé et de la Recherche Médicale UMR 1091, University of Nice Sophia Antipolis, 06100 Nice, France.
Didier F
DF
Pisani
Institute of Biology Valrose, Centre National de la Recherche Scientifique UMR 7277, Institut National de la Santé et de la Recherche Médicale UMR 1091, University of Nice Sophia Antipolis, 06100 Nice, France.
Jean-Claude
JC
Chambard
Institute of Biology Valrose, Centre National de la Recherche Scientifique UMR 7277, Institut National de la Santé et de la Recherche Médicale UMR 1091, University of Nice Sophia Antipolis, 06100 Nice, France.
Ez-Zoubir
EZ
Amri
Department of Pharmacology and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia Department of Pharmacology and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia.
Dana S
DS
Hutchinson
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE -0691 Stockholm, Sweden tore.bengtsson@su.se.
Tore
T
Bengtsson
D052437:Adipocytes, Brown / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D039902:Multipotent Stem Cells / Q000378:metabolism; D046912:Multiprotein Complexes / Q000502:physiology*; D010766:Phosphorylation; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011743:Pyrimidines / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D058667:Adrenergic beta-3 Receptor Agonists; D051272:Glucose Transporter Type 1; D007328:Insulin; D009025:Morpholines; D046912:Multiprotein Complexes; D011743:Pyrimidines; D022702:Receptors, Adrenergic, beta-3; C495678:Slc2a1 protein, mouse; C541932:Ku 0063794; C546843:mTOR protein, mouse; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D007545:Isoproterenol; D020123:Sirolimus