Berberine remodels adipose tissue to attenuate metabolic disorders by activating sirtuin 3

Dan Li1,2, Chao Yang2,3, Jian-zhong Zhu2, Eduardo Lopez4, Tian Zhang2, Qiang Tong4, Cheng Peng1, Li-gen Lin2
1 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
2 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China
3 Key Laboratory of Health Risk Factors for Seafood and Environment of Zhejiang Province, Institute of Innovation & Application, Zhejiang Ocean University, Zhoushan 316022, China
4 Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
Correspondence to: Cheng Peng:, Li-gen Lin:,
DOI: 10.1038/s41401-021-00736-y
Received: 6 March 2021
Accepted: 29 June 2021
Advance online: 20 August 2021


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.
Keywords: berberine; adipose tissue inflammation; fibrosis; liver injury; Sirtuin 3; insulin resistance

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