TY - JOUR AU - Li Dan AU - Yang Chao AU - Zhu Jian-zhong AU - Lopez Eduardo AU - Zhang Tian AU - Tong Qiang AU - Peng Cheng AU - Lin Li-gen PY - 2022 TI - Berberine remodels adipose tissue to attenuate metabolic disorders by activating sirtuin 3 JF - Acta Pharmacologica Sinica; Vol 43, No 5 (May 2022): Acta Pharmacologica Sinica Y2 - 2022 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/10566