State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China.
Shanghai Jiao Tong University, School of Pharmacy, 800 Dongchuan Road, Shanghai, 200240, China.
Biomed Pharmacother. 2019 Mar;111:99-108. doi: 10.1016/j.biopha.2018.12.059. Epub 2018 Dec 19.
The lack of valid therapeutic approach that can ameliorate the manifestations of NASH is a barrier to therapeutic development. Therefore, we investigate the novel role of Methyl Palmitate (MP) in preventing NASH and the possible mechanism involved.
50 Male C57BL/6 J mice were randomly divided into 5 groups (n = 10). The control group was fed control diet; model group was fed MCD diet; MP 1 group was fed MCD diet supplemented with MP (75 mg/kg/day); MP 2 group was fed MCD plus MP diet (150 mg/kg/day); and MP 3 group was fed MCD plus MP diet (300 mg/kg/day). Histological staining's, and commercially available kits for serum ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively.
Mice fed MCD diet developed NASH, which was markedly improved by MP in a dose-dependent manner. MP treatment improved hepatic content of TG, TC, MDA, SOD and GSH and serum levels of ALT and AST. In vivo studies showed that MP treatment activated PPARα expression, that in turns, promoted β-oxidation protein and gene expressions, suppressed TNFα, MCP1, TGFβ1 and Colla1 protein and gene expression levels, contributing to the prevention of NASH.
Our results indicated that MP could successfully prevent NASH. This effect of MP was mediated through induction of PPARα pathway. This study provides a novel therapeutic target that plays pivotal role in the prevention of NASH.
目前缺乏有效的治疗方法来改善 NASH 的临床表现，这是治疗发展的一个障碍。因此，我们研究了棕榈酸甲酯 (MP) 在预防 NASH 中的新作用及其可能涉及的机制。
50 只雄性 C57BL/6J 小鼠被随机分为 5 组（n=10）。对照组给予基础饮食；模型组给予 MCD 饮食；MP1 组给予 MCD 饮食+MP（75mg/kg/天）；MP2 组给予 MCD+MP 饮食（150mg/kg/天）；MP3 组给予 MCD+MP 饮食（300mg/kg/天）。采用组织学染色、商业试剂盒检测血清 ALT 和 AST 以及肝组织 TG、TC、MDA、SOD 和 GSH 的含量，评估 NASH。此外，通过 Western blot 和 qPCR 分别测定相对肝蛋白和基因表达水平。
给予 MCD 饮食的小鼠发生 NASH，MP 以剂量依赖性方式显著改善 NASH。MP 治疗可改善肝组织 TG、TC、MDA、SOD 和 GSH 含量及血清 ALT 和 AST 水平。体内研究表明，MP 治疗激活了 PPARα 的表达，进而促进了β-氧化蛋白和基因的表达，抑制了 TNFα、MCP1、TGFβ1 和 Colla1 蛋白和基因的表达水平，有助于预防 NASH。
我们的研究结果表明，MP 可成功预防 NASH。MP 的这种作用是通过诱导 PPARα 通路介导的。本研究为预防 NASH 提供了一个新的治疗靶点，发挥着关键作用。
