Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c
What this study shows
The authors deleted rictor, an essential mTORC2 component, only in mouse liver. In fed knockout mice the liver lost Akt Ser473 phosphorylation and had lower glucokinase and SREBP1c activity, so it kept making glucose (gluconeogenesis) while glycolysis and fat synthesis fell, as if it could not sense that the animal had eaten. The mice became hyperglycaemic and hyperinsulinaemic with low blood lipids. In mTORC2-deficient hepatocytes, constitutively active Akt2 restored both glucose flux and lipogenesis, while extra glucokinase restored glucose flux but not lipogenesis, placing Akt as the main route from hepatic mTORC2 to these outputs. Boundary: Mouse liver with lifelong genetic loss of mTORC2, plus cultured mouse hepatocytes. Not a drug study and not tested in people. Drafted from the abstract only.
At a glance
| Evidence type | A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Liver-specific rictor knockout mice (LiRiKO); primary hepatocytes with constitutively active Akt2 or glucokinase rescue); the code names the system studied -- animal work can be rigorous and still not be human data. |
| Study type | 4 - Animal Study |
| Model system | Liver-specific rictor knockout mice (LiRiKO); primary hepatocytes with constitutively active Akt2 or glucokinase rescue |
| Journal | Cell Metabolism |
| Year | 2012 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1016/j.cmet.2012.03.015 · PMID 22521878 |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Liver-specific rictor knockout (mTORC2 loss) |
| Target | Hepatic Akt Ser473, glucokinase, SREBP1c; glycolysis, lipogenesis, gluconeogenesis; blood glucose, insulin, lipids |
| Model | Mouse |
| Effect | Loss of hepatic mTORC2 lowers Akt signalling, glycolysis and lipogenesis and causes hyperglycaemia and hyperinsulinaemia |
In the Atlas
Related topics
Links in the pathway map
- Supports mTORC2 activates Akt/PKB
- Supports mTORC2 activates Lipid synthesis
More studies on this topic
- Impaired mTOR/SREBP1-Mediated Lipogenesis as a Mechanism of Hepatic Glycogen Accumulation in a Carnivorous Fish Model, Largemouth Bass (Micropterus salmoides) (2026)
- Activation of a metabolic gene regulatory network downstream of mTOR complex 1 (2010)
- Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity (2013)
- mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway (2011)
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