PPAR? attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation.

ABSTRACT: Peroxisome proliferator-activated receptor ? (PPAR?) belongs to the nuclear receptor family and is involved in metabolic diseases. Although PPAR? is known to attenuate hepatic lipid deposition, its mechanism remains unclear. Here, we show that PPAR? is a potent stimulator of hepatic autophagic flux. The expression levels of PPAR? and autophagy-related proteins were decreased in liver tissues from obese and ageing mice. Pharmacological and adenovirus-mediated increases in PPAR? expression and activity were achieved in obese transgenic db/db and high fat diet-fed mice. Using genetic, pharmacological and metabolic approaches, we demonstrate that PPAR? reduces intrahepatic lipid content and stimulates ?-oxidation in liver and hepatic cells by an autophagy-lysosomal pathway involving AMPK/mTOR signalling. These results provide novel insight into the lipolytic actions of PPAR? through autophagy in the liver and highlight its potential beneficial effects in NAFLD.

SUBMITTER: Tong L 

PROVIDER: S-EPMC6393554 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature