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Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway.
- Source :
-
Molecular nutrition & food research [Mol Nutr Food Res] 2015 Aug; Vol. 59 (8), pp. 1443-57. Date of Electronic Publication: 2015 May 28. - Publication Year :
- 2015
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Abstract
- Scope: Resveratrol (RSV), a natural polyphenol, has been reported to attenuate nonalcoholic fatty liver disease (NAFLD); however, its underlying mechanism is unclear. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, we investigated the role of autophagy in the beneficial effects of RSV on hepatic steatosis.<br />Methods and Results: Via Oil red O staining, triglyceride, and β-hydroxybutyrate detection, we found that RSV decreased palmitate-induced lipid accumulation and stimulated fatty acid β-oxidation in hepatocytes. Based on Western blot assay, confocal microscopy and transmission electron microscopy, we found that RSV induced autophagy in hepatocytes, whereas autophagy inhibition markedly abolished RSV-mediated hepatic steatosis improvement. Moreover, RSV increased cAMP levels and the levels of SIRT1 (sirtuin 1), pPRKA (phosphorylated protein kinase A), and pAMPK (phosphorylated AMP-activated protein kinase), as well as SIRT1 activity in HepG2 cells. Incubation with inhibitors of AC (adenylyl cyclase), PRKA, AMPK, SIRT1, or with AC, PRKA, AMPK, or SIRT1 siRNA abolished RSV-mediated autophagy. Similar results were obtained in mice with hepatic steatosis.<br />Conclusion: RSV improved hepatic steatosis partially by inducing autophagy via the cAMP-PRKA-AMPK-SIRT1 signaling pathway, which provides new evidence regarding RSV's effects on NAFLD treatment.<br /> (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Adenylyl Cyclases chemistry
Adenylyl Cyclases genetics
Adenylyl Cyclases metabolism
Animals
Antioxidants metabolism
Cyclic AMP antagonists & inhibitors
Cyclic AMP metabolism
Enzyme Induction drug effects
Enzyme Inhibitors pharmacology
Fatty Acids, Nonesterified adverse effects
Fatty Acids, Nonesterified antagonists & inhibitors
Fatty Acids, Nonesterified metabolism
Hep G2 Cells
Humans
Lipid Metabolism drug effects
Liver drug effects
Liver pathology
Liver ultrastructure
Mice, 129 Strain
Microscopy, Electron, Transmission
Non-alcoholic Fatty Liver Disease metabolism
Non-alcoholic Fatty Liver Disease pathology
RNA Interference
Resveratrol
Sirtuin 1 antagonists & inhibitors
Sirtuin 1 chemistry
Sirtuin 1 genetics
Sirtuin 1 metabolism
Stilbenes metabolism
Antioxidants therapeutic use
Autophagy drug effects
Cyclic AMP agonists
Dietary Supplements
Liver metabolism
Non-alcoholic Fatty Liver Disease diet therapy
Second Messenger Systems drug effects
Stilbenes therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1613-4133
- Volume :
- 59
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular nutrition & food research
- Publication Type :
- Academic Journal
- Accession number :
- 25943029
- Full Text :
- https://doi.org/10.1002/mnfr.201500016