PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation

Peroxisome proliferator-activated receptor delta (PPAR delta) belongs to the nuclear receptor family and is involved in metabolic diseases. Although PPARd is known to attenuate hepatic lipid deposition, its mechanism remains unclear. Here, we show that PPAR delta is a potent stimulator of hepatic autophagic flux. The expression levels of PPAR delta and autophagy-related proteins were decreased in liver tissues from obese and ageing mice. Pharmacological and adenovirus-mediated increases in PPAR delta 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 delta reduces intrahepatic lipid content and stimulates beta-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 delta through autophagy in the liver and highlight its potential beneficial effects in NAFLD.