Cited by 170Sirtuins and Resveratrol in MedicineLiver Disease Diagnosis and TreatmentAutophagy in Disease and Therapy

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

Zhang, Yong, Chen, Ming‐liang, Zhou, Yong, Yi, Long, Gao, Yan‐xiang, Ran, Li, Chen, Shi‐hui, Zhang, Ting +8 more·2015·Molecular Nutrition & Food Research

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. 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. 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.

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Crossref · 10.1002/mnfr.201500016

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Authors
Zhang, Y., Chen, M., Zhou, Y., Yi, L., Gao, Y., Ran, L., Chen, S., Zhang, T., Zhou, X., Zou, D., Wu, B., Wu, Y., Chang, H., Zhu, J., Zhang, Q., & Mi, M.
Affiliations
  • Army Medical University (CN)
  • Research Center for Nutrition and Food Safety Institute of Military Preventive Medicine Third Military Medical University Chongqing P. R. China
Venue
Molecular Nutrition & Food Research
Publisher
Wiley
Published
2015-05-28
Volume
59
Issue
8
Pages
1443-1457
ISSN
  • 1613-4125 (ISSN-L)
  • 1613-4133
OpenAlex
W1767926241
Cited by
170
References
56
Citations by year
2026: 8 · 2025: 9 · 2024: 14 · 2023: 13 · 2022: 12 · 2021: 19 · 2020: 22 · 2019: 16 · 2018: 22 · 2017: 16 · 2016: 16 · 2015: 3
FWCI
9.51
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Nutrition & Food Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (30972469, 81273059)
  • Technological Project of Chongqing (CSTC, 2011AB5040)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
resveratrol, hepatic steatosis, non-alcoholic fatty liver disease, autophagy, cAMP signaling, SIRT1, protein kinase A, AMPK, adenylate cyclase, fatty acid beta-oxidation, hepatocytes, polyphenols
MeSH terms
Resveratrol, Cyclic AMP, Adenylyl Cyclases, Animals, Antioxidants, Autophagy, Enzyme Induction, Enzyme Inhibitors, Fatty Acids, Nonesterified, Humans, Liver, Stilbenes, Second Messenger Systems, Dietary Supplements, RNA Interference, Microscopy, Electron, Transmission, Lipid Metabolism, Sirtuin 1, Hep G2 Cells, Mice, 129 Strain, Non-alcoholic Fatty Liver Disease

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