Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine
Open accessAbstract
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.
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Berberine acts as a SIRT1 or AMPK agonist to mimic energy restriction.
“For patients with T2DM, the main function of berberine is as a SIRT1 or AMPK agonist to mimic energy restriction [75–77] and to target on NF-κB [78] to improve insulin resistance and inflammation as well as to alleviate the activation of ox-LDL-induced macrophages [79].”
From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [75]
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- Authors
- Shan, Y., Zhang, S., Gao, B., Liang, S., Zhang, H., Yu, X., Zhao, J., Ye, L., Yang, Q., & Shang, W.
- Affiliations
- Nanjing University of Chinese Medicine (CN)
- University of California, Irvine (US)
- Corresponding author
- Shang, Wenbin
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2020-12-17
- Volume
- 11
- Pages
- 591227-591227
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC7774030
- OpenAlex
- W3112913802
- Cited by
- 49
- References
- 55
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 5 · 2023: 11 · 2022: 4 · 2021: 11
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (81873060, 81473391, 81603569)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- berberine, SIRT1, adipose tissue, insulin sensitivity, adipocyte glucose uptake, AMPK signaling, Akt phosphorylation, adipose tissue inflammation, macrophages, high-fat diet-induced obesity, Coptis chinensis, JNK, IKKβ, inflammatory cytokines
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