Dihydromyricetin contributes to weight loss via pro-browning mediated by mitochondrial fission in white adipose.
Dihydromyricetin contributes to weight loss via pro-browning mediated by mitochondrial fission in white adipose.
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DOI：
10.1016/j.ejphar.2022.175345
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发表时间：
2022-10
影响因子：
5
通讯作者：
Xiaowei Xiong;Min Xia;Ailin Niu;Yanan Zhang;Tingting Yin;Qiren Huang
中科院分区：
文献类型：
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作者：
Xiaowei Xiong;Min Xia;Ailin Niu;Yanan Zhang;Tingting Yin;Qiren Huang
二氢杨梅素（DHM）是从常用中草药显齿蛇葡萄中提取的一种天然黄酮类化合物。具有降血糖、降血脂、抗炎、抗氧化、保肝等多种药理作用。在这项研究中，我们阐明了它对线粒体动力学和白色脂肪的布朗宁的作用。在体内实验中，用正常饮食（ND）、高脂饮食（HFD）或HFD + DHM（250 mg/kg.d-1）灌胃喂养6周龄雄性C57 BL/6小鼠;在体外实验中，用不同浓度的DHM诱导和处理3 T3-L1和小鼠原代前脂肪细胞。对小鼠代谢表型、脂质蓄积、白色脂肪细胞的布朗宁和线粒体动力学进行了检测。结果发现，DHM治疗降低了肥胖小鼠的体重和脂肪量，改善了糖耐量、胰岛素抵抗和耐冷性。DHM处理增加了脂肪组织中经典棕色脂肪细胞标志物（UCP-1、PGC-1α、PRDM 16）和线粒体动力学相关蛋白（DRP 1、FIS 1、OPA 1、MFN 2）的表达。DHM诱导成熟的3 T3-L1细胞分化为棕色脂肪细胞，并增强线粒体动力学相关蛋白的表达。线粒体分裂抑制剂Mdivi-1可抑制DHM的促褐化作用。这些结果表明DHM处理通过促进线粒体分裂诱导白色脂肪的褐化重塑，并通过线粒体分裂介导的促褐化作用表现出抗肥胖特性，这意味着DHM可能在肥胖及相关疾病的预防和治疗中发挥重要作用。
Dihydromyricetin (DHM) is a natural bioactive flavonoid extracted from AmpelopsisGrossedentata, a commonly used Chinese herbal medicine. It has multiple beneficial pharmacological effects including lowering blood glucose and lipid, as well as anti-inflammation, anti-oxidation and hepato-protection. In this study, we elucidated its actions on mitochondrial dynamics and browning of white adipose. In the experimentsin vivo, six-week-old male C57BL/6 mice were fed with normal diet (ND), high-fat diet (HFD), or HFD with intragastric administration of DHM (250 mg/kg.d−1); in the experimentsin vitro, 3T3-L1 and mouse primary preadipocytes were induced and treated with various concentrations of DHM. The mouse metabolic phenotype, lipid accumulation, the browning and mitochondrial dynamics of white adipocytes were examined. It was found that DHM treatment reduced body weight and fat mass, improved glucose tolerance, insulin resistance and cold tolerance in mice with obesity. DHM treatment increased the expressions of classical brown adipocyte markers (UCP-1, PGC-1α, PRDM16) and mitochondrial dynamics-related proteins (DRP1, FIS1, OPA1, MFN2) in adipose tissue. Likewise, DHM treatment induced the differentiation of mature 3T3-L1 cells into brown-like adipocytes and also enhanced the expressions of mitochondrial dynamics-related proteinsin vitro. Moreover, the pro-browning effect of DHM can be abrogated by mitochondrial fission inhibitor Mdivi-1. These findings indicate that DHM treatment induces the browning-remodeling of white adipose by enhancing mitochondrial fission and manifests an anti-obesity property via pro-browning mediated by mitochondrial fission, which implies it may play important roles in prevention and therapy of obesity and related diseases.