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

ABSTRACT:

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.

Results

Sirt3^-/- mice fed a HFD presented exacerbated hepatic steatosis that was accompanied by decreased expression and DNA-binding activity of peroxisome proliferator-activated receptor (PPAR) α and of several of its target genes involved in fatty acid oxi

SUBMITTER: Barroso E 

PROVIDER: S-EPMC7488148 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature