Hepatic mTORC2 Activates Glycolysis and Lipogenesis through Akt, Glucokinase, and SREBP1c

Liver-specific knockout of mTORC2 in mice resulted in loss of Akt Ser473 phosphorylation and metabolic dysregulation.

• LiRiKO mice exhibited reduced activity of glucokinase and SREBP1c in the liver.
• The absence of mTORC2 led to increased gluconeogenesis and reduced glycolysis and lipogenesis.
• Mice with hepatic mTORC2 deficiency experienced systemic hyperglycemia, hyperinsulinemia, and hypolipidemia.
• Activation of Akt2 in mTORC2-deficient liver cells restored glucose flux and lipogenesis.
• Overexpression of glucokinase improved glucose flux but did not affect lipogenesis.

AI simplified