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Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD
BACKGROUND: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214131/ https://www.ncbi.nlm.nih.gov/pubmed/37252281 http://dx.doi.org/10.1016/j.jgr.2020.07.005 |
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author | Yang, Zehong Yu, Yuanyuan Sun, Nannan Zhou, Limian Zhang, Dong Chen, HaiXin Miao, Wei Gao, Weihang Zhang, Canyang Liu, Changhui Yang, Xiaoying Wu, Xiaojie Gao, Yong |
author_facet | Yang, Zehong Yu, Yuanyuan Sun, Nannan Zhou, Limian Zhang, Dong Chen, HaiXin Miao, Wei Gao, Weihang Zhang, Canyang Liu, Changhui Yang, Xiaoying Wu, Xiaojie Gao, Yong |
author_sort | Yang, Zehong |
collection | PubMed |
description | BACKGROUND: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. METHODS: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. RESULTS: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. CONCLUSION: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD. |
format | Online Article Text |
id | pubmed-10214131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-102141312023-05-27 Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD Yang, Zehong Yu, Yuanyuan Sun, Nannan Zhou, Limian Zhang, Dong Chen, HaiXin Miao, Wei Gao, Weihang Zhang, Canyang Liu, Changhui Yang, Xiaoying Wu, Xiaojie Gao, Yong J Ginseng Res Research Article BACKGROUND: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. METHODS: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. RESULTS: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. CONCLUSION: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD. Elsevier 2023-05 2020-08-04 /pmc/articles/PMC10214131/ /pubmed/37252281 http://dx.doi.org/10.1016/j.jgr.2020.07.005 Text en © 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Yang, Zehong Yu, Yuanyuan Sun, Nannan Zhou, Limian Zhang, Dong Chen, HaiXin Miao, Wei Gao, Weihang Zhang, Canyang Liu, Changhui Yang, Xiaoying Wu, Xiaojie Gao, Yong Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD |
title | Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD |
title_full | Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD |
title_fullStr | Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD |
title_full_unstemmed | Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD |
title_short | Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD |
title_sort | ginsenosides rc, as a novel sirt6 activator, protects mice against high fat diet induced nafld |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214131/ https://www.ncbi.nlm.nih.gov/pubmed/37252281 http://dx.doi.org/10.1016/j.jgr.2020.07.005 |
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