Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6.
Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6.
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DOI：
10.2147/dddt.s384884
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Xue Y
中科院分区：
文献类型：
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作者：
Li R;Ye Z;She D;Fang P;Zong G;Hu K;Kong D;Xu W;Li L;Zhou Y;Zhang K;Xue Y
虽然非酒精性脂肪性肝病（NAFLD）的发病机制已被广泛研究，但其潜在发病机制的作用仍不清楚，目前还没有批准的NAFLD治疗策略。本研究的目的是观察参麦灵在体内和体外对NAFLD的有益作用，并探讨其潜在的分子机制。用赛米控治疗2型糖尿病（T2 DM）合并非酒精性脂肪肝（NAFLD）小鼠12周。采用肝功能、血脂、肝脂、H&E染色、油红染色、天狼星染色等方法评价肝功能和肝结构。通过qPCR和Western blotting在体内和体外测量α/β水解酶结构域-6（ABHD 6）的表达。然后，进行双荧光素酶报告基因测定以验证上游miR-5120对ABHD 6的调控。我们的数据显示，Semaldehyde给药显著改善了T2 DM合并NAFLD小鼠的肝功能和肝脏脂肪变性。此外，与对照组相比，在T2 DM +NAFLD小鼠的肝脏和HG+ FFA刺激的Hepa 1-6肝细胞中发现ABHD 6上调和miR-5120下调。有趣的是，在Semenoid干预后，T2 DM +NAFLD小鼠肝脏和HG+ FFA刺激的Hepa 1-6肝细胞中ABHD 6表达显著降低，而miR-5120表达增加。我们还发现miR-5120可以调节ABHD 6在肝细胞中的表达，而Semanti可以通过miR-5120调节ABHD 6的表达。此外，GLP-1 R在小鼠肝组织和Hepa 1-6细胞中广泛表达。Semiphrine可通过GLP-1 R调节miR-5120/ABHD 6的表达。我们的数据揭示了Semalone改善T2 DM +NAFLD肝脂肪变性的潜在机制，并可能揭示miR-5120/ABHD 6在T2 DM +NAFLD发病机制中的病理作用。
Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of α/β hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1–6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1–6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1–6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.