Glucose uptake in brown fat cells is dependent on mTOR complex 2–promoted GLUT1 translocation

• DOI: 10.1083/jcb.201403080
• Publication Date: 2014-11-10T17:41:42Z
• Authors: Jessica M. Olsen; Masaaki Sato; Olof S. Dallner; Anna L. Sandström; Didier F. Pisani; Jean-Claude Chambard; Ez-Zoubir Amri; Dana S. Hutchinson; Tore Bengtsson
• Keywords: Male; MESH: Protein Transport; Morpholines; Primary Cell Culture; MESH: Morpholines; Adrenergic beta-3 Receptor Agonists; MESH: Insulin; Mechanistic Target of Rapamycin Complex 2; MESH: Isoproterenol; MESH: Primary Cell Culture; Mice; 03 medical and health sciences; [SDV.BDD] Life Sciences [q-bio]/Development Biology; Animals; Humans; Insulin; MESH: Animals; Phosphorylation; MESH: Mice; [SDV.BDD]Life Sciences [q-bio]/Development Biology; MESH: TOR Serine-Threonine Kinases; Research Articles; Cells, Cultured; MESH: Adipocytes, Brown; Glucose Transporter Type 1; 0303 health sciences; MESH: Humans; MESH: Phosphorylation; Multipotent Stem Cells; MESH: Adrenergic beta-3 Receptor Agonists; Isoproterenol; MESH: Multiprotein Complexes; MESH: Male; MESH: Glucose; Protein Transport; Adipocytes, Brown; Glucose; MESH: Protein Processing, Post-Translational; MESH: Pyrimidines; Multiprotein Complexes; Female; MESH: Sirolimus; MESH: Multipotent Stem Cells; MESH: Receptors, Adrenergic, beta-3; MESH: Female; Protein Processing, Post-Translational; MESH: Cells, Cultured; MESH: Glucose Transporter Type 1

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.