Berberine Remodels Adipose Tissue To Attenuate Metabolic Disorders by Activating Sirtuin 3

Authors

Dan Li
Chao Yang
Jian-Zhong Zhu
Eduardo Lopez
Tian Zhang
Qiang Tong
Cheng Peng
Li-Gen Lin

Publication Date

5-1-2022

Journal

Acta Pharmacologica Sinica

DOI

10.1038/s41401-021-00736-y

PMID

34417576

PMCID

PMC9061715

PubMedCentral® Posted Date

8-20-2021

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Adipose Tissue, Animals, Berberine, Diet, High-Fat, Inflammation, Insulin Resistance, Mice, MicroRNAs, Obesity, Sirtuin 3, berberine, adipose tissue inflammation, fibrosis, liver injury, Sirtuin 3, insulin resistance.

Abstract

Adipose tissue remodelling is considered a critical pathophysiological hallmark of obesity and related metabolic diseases. Berberine (BBR), a natural isoquinoline alkaloid, has potent anti-hyperlipidaemic and anti-hyperglycaemic effects. This study aimed to explore the role of BBR in modulating adipose tissue remodelling and the underlying mechanisms. BBR protected high fat diet (HFD)-fed mice against adiposity, insulin resistance and hyperlipidemia. BBR alleviated adipose tissue inflammation and fibrosis by inhibiting macrophage infiltration, pro-inflammatory macrophage polarization and the abnormal deposition of extracellular matrix, and the effect was mediated by BBR directly binding and activating the deacetylase Sirtuin 3 (SIRT3) and suppressing the activation of the mitogen-activated protein kinases and nuclear factor-κB signalling pathways. Furthermore, BBR decreased microRNA-155-5p secretion by macrophages, which in turn ameliorated liver injury. Moreover, BBR mitigated inflammatory responses in both LPS-stimulated macrophages and TNF-α-treated adipocytes and suppressed macrophage migration towards adipocytes by activating SIRT3. Collectively, this study revealed that BBR improved adipose tissue remodelling, and subsequently inhibited the secretion of microRNA-155-5p by macrophages, which alleviated adiposity, insulin resistance and liver injury in obese mice. The modulation of adipose tissue remodelling by activating SIRT3 could contribute to the anti-hyperlipidemic and anti-hyperglycemic effects of BBR.