SIRT3 deficiency exacerbates fatty liver by attenuating the HIF1α-LIPIN 1 pathway and increasing CD36 through Nrf2.

Background: Deficiency of mitochondrial sirtuin 3 (SIRT3), a NAD-dependent protein deacetylase that maintains redox status and lipid homeostasis, contributes to hepatic steatosis. In this study, we investigated additional mechanisms that might play a role in aggravating hepatic steatosis in Sirt3-deficient mice fed a high-fat diet (HFD).

Methods: Studies were conducted in wild-type (WT) and Sirt3 mice fed a standard diet or a HFD and in SIRT3-knockdown human Huh-7 hepatoma cells.