Figure 10: A model of RICTOR/mTORC2 function in adipocytes.
From: Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism
(1) In adipocytes, mTORC2 phosphorylates AKT in the hydrophobic motif (S473 in AKT1; S474 in AKT2) while PDK1 phosphorylates AKT in the kinase domain (T308 in AKT1; T309 in AKT2), which promotes maximal AKT activity. This includes stimulating GLUT4 translocation to the plasma membrane by inhibiting AS160. (2) By deleting Rictor in mature adipocytes, we provide evidence that Rictor/mTORC2 is not essential for AKT signalling to AS160 and other classic substrates, but it is required for normal glucose uptake and ChREBP activity. This suggests mTORC2 might only be essential for a specific AKT-target other than AS160 that promotes glucose uptake; or alternatively, mTORC2 may regulate glucose uptake by an AKT-independent mechanism (also see Discussion). (3) Furthermore, mTORC2-dependent glucose uptake drives ChREBP-dependent DNL and the production of a signal(s) that (4) promotes hepatic insulin sensitivity and possibly (5) HFD-induced adipogenesis. (6) Prolonged Rictor loss may lead to additional defects such as increased lipolysis.
