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PPARδ Attenuates Hepatic Steatosis Through the Autophagy-Mediated Fatty Acid Oxidation
43 Pages Posted: 2 Oct 2018
More...Abstract
Peroxisome proliferative associated receptor δ(PPARδ)belongs to the nuclear receptor family and has been found to involve in metabolic diseases. Although PPARδ is known to attenuate hepatic lipid deposition, its mechanism remain unclear. Here, we show that PPARδ is a potent stimulator of hepatic autophagic flux. Expression levels of PPARδ and autophagy markers were detected in liver tissues of obese and lean mice by western blot. Hepatic PPARδ expression decreased in obese mice in comparison to lean control, and the same findings were acquired in autophagy-related proteins (ATGs). Pharmacological or adenovirus-mediated promotion of PPARδ was applied in obese transgenetic 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 by an autophagy-lysosomal pathway. These results provide a novel insight into PPARδ's lipolytic actions through autophagy in liver and display its potential beneficial effects in NAFLD.
Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81570719, 81670797 81471074, 81770863, 81500660), partly supported by Key Laboratory for Endocrine and Metabolic Diseases, Chinese Ministry of Public Health (No. 1994DP131044), Ministry of Science & Technology Innovation Fund and projects (No.2011YQ030114), the Basic Important Program (No.10JC141100), the Sector Funds of Ministry of Health (No. 201002002), and the National Key New Drug Creation and Manufacturing Program by
Declaration of Interests: The authors declare that they have no conflict of interests.
Ethics Approval Statement: The animal protocol were reviewed and approved by the Animal Care Committee of Shanghai Jiao Tong University School of Medicine.
Keywords: PPARδ, autophagy, NAFLD, fatty acid oxidation
Suggested Citation: Suggested Citation