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Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway
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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“Moreover, RSV is a well-known activator of SIRT1 and our previous study also found that RSV improved hepatic steatosis partially by inducing autophagy via the SIRT1 signaling pathway in vitro and in vivo (36–38).”
In the citing paper
“Moreover, RSV is a well-known activator of SIRT1 and our previous study also found that RSV improved hepatic steatosis partially by inducing autophagy via the SIRT1 signaling pathway in vitro and in vivo (36–38).”
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Metadata
- 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 › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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