QSHY Granules Promote White Adipose Tissue Browning and Correct BCAAs Metabolic Disorder in NAFLD Mice.
QSHY Granules Promote White Adipose Tissue Browning and Correct BCAAs Metabolic Disorder in NAFLD Mice.
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DOI：
10.2147/dmso.s332659
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zhao Y
中科院分区：
文献类型：
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作者：
Zhang B;Ni M;Li X;Liu Q;Hu Y;Zhao Y
白色脂肪组织（WAT）对外周代谢参数和肝脏能量代谢有积极影响。目的从支链氨基酸（BCAA）催化作用和WAT布朗宁两方面探讨祛湿化瘀颗粒治疗非酒精性脂肪性肝病（NALFD）小鼠的药理作用机制。将30只C57 BL/6 J小鼠随机分为对照组（对照组）、NAFLD模型组（高脂高糖组）和QSHY颗粒治疗组（高脂高糖+QSHY组）。HFHS+QSHY组小鼠经口灌胃QSHY颗粒6周。评估代谢参数，观察循环和粪便中BCAA含量，并收集肝脏和附睾WAT（eWAT）进行病理学、定量实时聚合酶链反应和蛋白质印迹分析。与HFHS组相比，HFHS+QSHY组小鼠表现出恢复肝脏组织学变化，改善肝细胞脂肪变性，减轻炎性细胞浸润。QSHY颗粒能显著降低HFHS诱导的NAFLD小鼠肝脏甘油三酯和血清丙氨酸氨基转移酶的升高水平，减轻高胆固醇血症和胰岛素抵抗。此外，它纠正了HFHS小鼠血清和粪便中BCAA代谢紊乱，并促进HFHS小鼠eWAT中BCAA分解代谢基因的表达。QSHY颗粒还增加磷酸化AMP激活蛋白激酶（AMPK）蛋白的表达，上调eWAT中AMPK/SIRT 1/UCP-1途径的蛋白表达。QSHY颗粒改善NAFLD小鼠肝脏脂肪变性，纠正BCAA紊乱，其机制可能与调节AMPK/SIRT 1/UCP-1通路，促进WAT布朗宁有关。
White adipose tissue (WAT) has positive effects on peripheral metabolism parameters and liver energy metabolism. This study aimed to explain the pharmacological mechanism of Qushi Huayu (QSHY) granules in the treatment of nonalcoholic fatty liver disease (NALFD) mice based on branched-chain amino acid (BCAA) catabolism and WAT browning. Thirty C57BL/6J mice were randomly divided into a (Ctrl) control group, fed with a control diet, a NAFLD model group, fed with a high-fat and high-sugar (HFHS) diet, and a QSHY granules treatment (HFHS+QSHY) group, administered with QSHY granules. After 14 weeks of feeding, HFHS+QSHY group mice were administered QSHY granules through oral gavage for 6 weeks. The metabolic parameters were assessed, the circular and fecal BCAA content was observed, and liver and epididymal WAT (eWAT) were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses. Compared with the HFHS group, mice in the HFHS+QSHY group demonstrated restored liver histological changes, ameliorated hepatocyte steatosis, and alleviated inflammatory cell infiltration. Consistent with the pathological changes, QSHY granules significantly reduced the elevated levels of liver triglycerides, and serum alanine aminotransferase, and it relieved hypercholesterolemia and insulin resistance in mice with HFHS-induced NAFLD. Furthermore, it corrected BCAA metabolic disorders in serum and feces and promoted the expression of BCAA catabolic genes in the eWAT of HFHS mice. QSHY granules also increased the expression of phosphorylated AMP-activated protein kinase (AMPK) protein, up-regulating the protein expression of the AMPK/SIRT1/UCP-1 pathway in the eWAT. QSHY granules improved hepatic steatosis and corrected the BCAA disorder in NAFLD mice, and the related mechanisms regulated the AMPK/SIRT1/UCP-1 pathway and promoted WAT browning.