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Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine
Berberine (BBR), which is an active component of Coptis chinensis Franch, has been reported to improve glucose metabolism and insulin resistance in animal and human studies, predominantly via activation of the 5′-adenosine monophosphate kinase (AMPK) pathway and suppression of the inflammation respo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774030/ https://www.ncbi.nlm.nih.gov/pubmed/33390968 http://dx.doi.org/10.3389/fphar.2020.591227 |
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author | Shan, Yun Zhang, Shuchen Gao, Bin Liang, Shu Zhang, Hao Yu, Xizhong Zhao, Juan Ye, Lifang Yang, Qin Shang, Wenbin |
author_facet | Shan, Yun Zhang, Shuchen Gao, Bin Liang, Shu Zhang, Hao Yu, Xizhong Zhao, Juan Ye, Lifang Yang, Qin Shang, Wenbin |
author_sort | Shan, Yun |
collection | PubMed |
description | Berberine (BBR), which is an active component of Coptis chinensis Franch, has been reported to improve glucose metabolism and insulin resistance in animal and human studies, predominantly via activation of the 5′-adenosine monophosphate kinase (AMPK) pathway and suppression of the inflammation response. However, the mechanisms underlying the effects of BBR on AMPK and inflammation remain unclear. In this present study, we found that BBR upregulated SIRT1 expression in 3T3L-1 adipocytes and adipose tissue. Inhibition of SIRT1 blunted the BBR-induced increase in glucose consumption and uptake in adipocytes. The BBR-induced activation of the AMPK pathway and AKT phosphorylation in adipocytes and adipose tissue were also attenuated by inhibition or knockout of Sirt1. The BBR-induced improvement of systemic insulin sensitivity was impaired by Sirt1 knockout in HFD-induced obese mice. The suppressing effects of BBR on systemic and local inflammatory responses, such as serum concentrations and expression of inflammatory cytokines, phosphorylation of c-Jun N-terminal kinase (JNK) and IKKβ, and the accumulation of F4/80-positive macrophages in adipose tissue were also attenuated in Sirt1 knockout mice. The BBR-induced decrease in PGC-1α acetylation was reversed by inhibition or knockout of Sirt1 in adipocytes and adipose tissue. Together, these results indicate that adipose tissue SIRT1 is a key regulator of the insulin sensitizing and anti-inflammatory effects of BBR, which contributes to the improvement of metabolic dysregulation. |
format | Online Article Text |
id | pubmed-7774030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77740302021-01-01 Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine Shan, Yun Zhang, Shuchen Gao, Bin Liang, Shu Zhang, Hao Yu, Xizhong Zhao, Juan Ye, Lifang Yang, Qin Shang, Wenbin Front Pharmacol Pharmacology Berberine (BBR), which is an active component of Coptis chinensis Franch, has been reported to improve glucose metabolism and insulin resistance in animal and human studies, predominantly via activation of the 5′-adenosine monophosphate kinase (AMPK) pathway and suppression of the inflammation response. However, the mechanisms underlying the effects of BBR on AMPK and inflammation remain unclear. In this present study, we found that BBR upregulated SIRT1 expression in 3T3L-1 adipocytes and adipose tissue. Inhibition of SIRT1 blunted the BBR-induced increase in glucose consumption and uptake in adipocytes. The BBR-induced activation of the AMPK pathway and AKT phosphorylation in adipocytes and adipose tissue were also attenuated by inhibition or knockout of Sirt1. The BBR-induced improvement of systemic insulin sensitivity was impaired by Sirt1 knockout in HFD-induced obese mice. The suppressing effects of BBR on systemic and local inflammatory responses, such as serum concentrations and expression of inflammatory cytokines, phosphorylation of c-Jun N-terminal kinase (JNK) and IKKβ, and the accumulation of F4/80-positive macrophages in adipose tissue were also attenuated in Sirt1 knockout mice. The BBR-induced decrease in PGC-1α acetylation was reversed by inhibition or knockout of Sirt1 in adipocytes and adipose tissue. Together, these results indicate that adipose tissue SIRT1 is a key regulator of the insulin sensitizing and anti-inflammatory effects of BBR, which contributes to the improvement of metabolic dysregulation. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7774030/ /pubmed/33390968 http://dx.doi.org/10.3389/fphar.2020.591227 Text en Copyright © 2020 Shan, Zhang, Gao, Liang, Zhang, Yu, Zhao, Ye, Yang and Shang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Shan, Yun Zhang, Shuchen Gao, Bin Liang, Shu Zhang, Hao Yu, Xizhong Zhao, Juan Ye, Lifang Yang, Qin Shang, Wenbin Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine |
title | Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine |
title_full | Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine |
title_fullStr | Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine |
title_full_unstemmed | Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine |
title_short | Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine |
title_sort | adipose tissue sirt1 regulates insulin sensitizing and anti-inflammatory effects of berberine |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774030/ https://www.ncbi.nlm.nih.gov/pubmed/33390968 http://dx.doi.org/10.3389/fphar.2020.591227 |
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