Shan Yun, Zhang Shuchen, Gao Bin, Liang Shu, Zhang Hao, Yu Xizhong, Zhao Juan, Ye Lifang, Yang Qin, Shang Wenbin
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2020 Dec 17;11:591227. doi: 10.3389/fphar.2020.591227. eCollection 2020.
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 . The BBR-induced improvement of systemic insulin sensitivity was impaired by 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 knockout mice. The BBR-induced decrease in PGC-1α acetylation was reversed by inhibition or knockout of 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.
黄连素（BBR）是黄连的一种活性成分，动物和人体研究报告显示，它主要通过激活5'-腺苷单磷酸激酶（AMPK）途径和抑制炎症反应来改善葡萄糖代谢和胰岛素抵抗。然而，BBR对AMPK和炎症作用的潜在机制仍不清楚。在本研究中，我们发现BBR上调了3T3L-1脂肪细胞和脂肪组织中SIRT1的表达。抑制SIRT1可减弱BBR诱导的脂肪细胞葡萄糖消耗和摄取增加。抑制或敲除SIRT1也会减弱BBR诱导的脂肪细胞和脂肪组织中AMPK途径的激活以及AKT磷酸化。在高脂饮食诱导的肥胖小鼠中，敲除SIRT1会损害BBR诱导的全身胰岛素敏感性改善。在敲除SIRT1的小鼠中，BBR对全身和局部炎症反应的抑制作用也会减弱，如血清炎症因子浓度和表达、c-Jun氨基末端激酶（JNK）和IKKβ的磷酸化，以及脂肪组织中F4/80阳性巨噬细胞的积累。抑制或敲除脂肪细胞和脂肪组织中的SIRT1可逆转BBR诱导的PGC-1α乙酰化降低。总之，这些结果表明脂肪组织SIRT1是BBR胰岛素增敏和抗炎作用的关键调节因子，有助于改善代谢失调。
