Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability.

ABSTRACT: Increased hepatic lipid content is an early correlate of insulin resistance and can be caused by nutrient-induced activation of mammalian target of rapamycin (mTor). This activation of mTor increases basal Akt activity, leading to a self-perpetuating lipogenic cycle. We have previously shown that the developmental Notch pathway has metabolic functions in adult mouse liver. Acute or chronic inhibition of Notch dampens hepatic glucose production and increases Akt activity and may therefore be predicted to increase hepatic lipid content. Here we now show that constitutive liver-specific ablation of Notch signaling, or its acute inhibition with a decoy Notch1 receptor, prevents hepatosteatosis by blocking mTor complex 1 (mTorc1) activity. Conversely, Notch gain of function causes fatty liver t

SUBMITTER: Pajvani UB 

PROVIDER: S-EPMC3737382 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature