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

J Cell Biol. 2014 Nov 10;207(3):365-74. doi: 10.1083/jcb.201403080.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / metabolism*
  • Adrenergic beta-3 Receptor Agonists / pharmacology
  • Animals
  • Cells, Cultured
  • Female
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Insulin / pharmacology
  • Insulin / physiology
  • Isoproterenol / pharmacology
  • Male
  • Mechanistic Target of Rapamycin Complex 2
  • Mice
  • Morpholines / pharmacology
  • Multipotent Stem Cells / metabolism
  • Multiprotein Complexes / physiology*
  • Phosphorylation
  • Primary Cell Culture
  • Protein Processing, Post-Translational
  • Protein Transport
  • Pyrimidines / pharmacology
  • Receptors, Adrenergic, beta-3 / metabolism
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / physiology*


  • Adrenergic beta-3 Receptor Agonists
  • Glucose Transporter Type 1
  • Insulin
  • Morpholines
  • Multiprotein Complexes
  • Pyrimidines
  • Receptors, Adrenergic, beta-3
  • Slc2a1 protein, mouse
  • Ku 0063794
  • mTOR protein, mouse
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases
  • Glucose
  • Isoproterenol
  • Sirolimus