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Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway.

Authors :
Zhang Y
Chen ML
Zhou Y
Yi L
Gao YX
Ran L
Chen SH
Zhang T
Zhou X
Zou D
Wu B
Wu Y
Chang H
Zhu JD
Zhang QY
Mi MT
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

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.)

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