Blocking Notch reduces liver fat buildup by lowering mTorc1 stability and disconnecting it from Akt activation

Constitutive liver-specific ablation of Notch signaling prevents hepatosteatosis by blocking mTor complex 1 (mTorc1) activity.

• Increased hepatic lipid content is associated with insulin resistance and can be triggered by nutrient-induced mTor activation.
• Acute or chronic inhibition of Notch signaling reduces hepatic glucose production and may increase Akt activity.
• Notch gain of function leads to fatty liver through sustained activation of mTorc1.
• Treatment with rapamycin can reverse the fatty liver effect caused by Notch activation.
• Notch signaling enhances mTorc1 complex stability, which promotes lipogenesis via the Srebp1c pathway.

Simplified