PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation

Cell Death & Disease
Lei TongZhiguo Zhang

Abstract

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

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Citations

Jan 25, 2020·Phytotherapy Research : PTR·Muhammad Torequl IslamMohammad S Mubarak
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Methods Mentioned

BETA
fluorescence microscopy
electron microscopy
PCR
confocal microscopy
light microscopy
PMH
transfection

Software Mentioned

AlphaView
GraphPad
SPSS
GraphPad Prism

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