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小檗碱通过激活 AMPK 信号通路减轻高脂饮食诱导肥胖小鼠的脂肪组织纤维化。

Berberine alleviates adipose tissue fibrosis by inducing AMP-activated kinase signaling in high-fat diet-induced obese mice.

机构信息

Zhejiang Provincial People's Hospital, Hangzhou, No.158 shangtang road, Zhejiang, PR China; People's Hospital of Hangzhou Medical College, Hangzhou, No.481 binwen road, Zhejiang, PR China.

出版信息

Biomed Pharmacother. 2018 Sep;105:121-129. doi: 10.1016/j.biopha.2018.05.110. Epub 2018 May 28.

Abstract

Adipose tissue fibrosis is a novel mechanism for the development of obesity related insulin resistance. Berberine (BBR) has been shown to relieve several metabolic disorders, including obesity and type 2 diabetes. However, the effects of BBR on obesity related adipose fibrosis remain poorly understood. The objective of this study was to assess the effects of BBR on adipose tissue fibrosis in high fat diet (HFD)-induced obese mice. The results showed that BBR reduced animal body weight and significantly improved glucose tolerance in HFD mice. In addition, BBR treatment markedly attenuated collagen deposition and reversed the up-regulation of fibrosis associated genes in the adipose tissue of HFD mice. Moreover, BBR treatment activated AMP-activated kinase signaling and reduced TGF-β1 and Smad3 phosphorylation. Of note, the inhibitory effects of BBR on adipose tissue fibrosis were significantly blocked by AMPK inhibition with compound C, an AMPK inhibitor. Macrophage infiltration and polarization induced by HFD were also reversed after BBR administration. These findings suggest that BBR displays beneficial effects in the treatment of obesity, in part via improvement of adipose tissue fibrosis.

摘要

脂肪组织纤维化是肥胖相关胰岛素抵抗发展的一种新机制。小檗碱(BBR)已被证明可缓解多种代谢紊乱,包括肥胖和 2 型糖尿病。然而,BBR 对肥胖相关脂肪纤维化的影响仍知之甚少。本研究旨在评估 BBR 对高脂肪饮食(HFD)诱导肥胖小鼠脂肪组织纤维化的影响。结果表明,BBR 可降低动物体重,并显著改善 HFD 小鼠的葡萄糖耐量。此外,BBR 治疗可显著减轻胶原沉积,并逆转 HFD 小鼠脂肪组织中与纤维化相关基因的上调。此外,BBR 治疗可激活 AMP 激活的蛋白激酶信号通路,并减少 TGF-β1 和 Smad3 的磷酸化。值得注意的是,用 AMPK 抑制剂复合物 C 抑制 AMPK 可显著阻断 BBR 对脂肪组织纤维化的抑制作用。BBR 给药后还可逆转 HFD 诱导的巨噬细胞浸润和极化。这些发现表明,BBR 通过改善脂肪组织纤维化在肥胖症的治疗中显示出有益的作用。

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