Berberine attenuates the abnormal ectopic lipid deposition in skeletal muscle
Berberine attenuates the abnormal ectopic lipid deposition in skeletal muscle
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小檗碱减轻骨骼肌中异常的异位脂质沉积
DOI：
10.1016/j.freeradbiomed.2020.07.028
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发表时间：
2020
影响因子：
7.4
通讯作者：
Zhang Zhiguo
中科院分区：
文献类型：
--
作者：
Yao Shuangshuang;Yuan Yini;Zhang Huizhi;Meng Xiangjian;Jin Lina;Yang Jian;Wang Weiqing;Ning Guang;Zhang Yifei;Zhang Zhiguo
背景非脂肪组织中的脂质沉积与肥胖倾向有关。骨骼肌线粒体功能障碍，证明不完全β氧化可能有助于异位脂质沉积在高脂肪饮食诱导的肥胖症。小檗碱（BBR）已被证明具有改善肥胖或2型糖尿病患者代谢紊乱的特性。方法用小檗碱处理小鼠，分析其代谢特征。观察小檗碱对线粒体数量和功能的影响。在RNA干扰或腺病毒感染后，验证腺苷5 '-单磷酸激活蛋白激酶（AMPK）/过氧化物酶体增殖物激活受体-γ共激活因子1α（PGC-1α）的作用。结果在本研究中，我们研究了小檗碱对骨骼肌脂质沉积的影响，发现小檗碱在体内和体外都能增加线粒体的数量和功能。此外，小檗碱还通过AMPK途径促进PGC-1α的表达，PGC-1 α是与线粒体生物发生和功能相关的关键转录辅激活因子。小檗碱可降低C2 C12心肌细胞的基础耗氧率（OCR），提高最大耗氧率，提示小檗碱可增强线粒体的潜在功能。
BackgroundLipid deposition in non-adipose tissue is associated with a propensity to obesity. Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation may contribute to ectopic lipid deposition during high fat diet-induced obesity. Berberine (BBR) has been proved to possess the properties of improving metabolic disorders in patients with obesity or type 2 diabetes mellitus. However, the precise mechanism remains obscure.MethodsMice were treated with berberine and metabolic profile were analyzed. Mitochondrial number and function were detected after berberine treatment in vitro and in vivo. The role of Adenosine 5‘-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was verified after RNA interference or adenovirus infection.ResultsIn the current study, we investigated the influence of berberine on the lipid deposition of skeletal muscle and found that berberine could increase the mitochondrial number and function both in vivo and in vitro. Furthermore, berberine promoted the expression of PGC-1α, the crucial transcriptional coactivator related to mitochondrial biogenesis and function, through AMPK pathway. Berberine reduced the basal oxygen consumption rates (OCR) but increased the maximal OCR in C2C12 myocytes, which indicated that berberine could increase the potential function of mitochondria.ConclusionOur results proved that berberine can protect the lean body mass from excessive lipid accumulation, by promoting the mitochondrial biogenesis and improving fatty acid oxidation in an AMPK/PGC-1α dependent manner.