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 beta3-adrenoceptor-stimulated glucose uptake in brown adipose tissue. We show that beta3-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 beta3-adrenoceptor-stimulated glucose uptake. Importantly, the effect of beta3-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.
Olsen, J. M., Sato, M., Dallner, O. S., Sandstrom, A. L., Pisani, D. F., Chambard, J-C., Amri, E-Z., Hutchinson, D. S., & Bengtsson, T. (2014). Glucose uptake in brown fat cells is dependent on mTOR complex 2-promoted GLUT1 translocation. Journal of Cell Biology, 207(3), 365 - 374. https://doi.org/10.1083/jcb.201403080