Xuan Qiu, Lei Yu, Si-Yu Tian, Ya-Jie Chen, Hong-Ling Yan, Kuan-Zhi Liu
{"title":"[α-硫辛酸通过激活AMPK/mTOR通路改善2型糖尿病大鼠肝损伤]。","authors":"Xuan Qiu, Lei Yu, Si-Yu Tian, Ya-Jie Chen, Hong-Ling Yan, Kuan-Zhi Liu","doi":"10.12047/j.cjap.6312.2022.098","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of α-lipoic acid in ameliorating liver injury in rats with type 2 diabetes mellitus <i>via</i> activating adenosine 5'-monophosphate-activate protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.</p><p><strong>Methods: </strong>The T2DM rat models were established by feeding with high-fat, high-sucrose diet and intraperitoneal injection of 27.5 mg/(kg·d) streptozotocin. The 32 rats with T2DM were randomly divided into 4 groups: T2DM group, α-lipoic acid group (LA), Compound C group (Comp C, an inhibitor of AMPK) and LA+Comp C group, with 8 rats in each group. Additionally, 8 Sprague-Dawlay (SD) rats without diabetes were set as normal control. The rats received α-lipoic acid at a dosage of 100 mg/(kg·d) or Compound C at a dosage of 20 mg/(kg·d) by intraperitoneal injection for 8 weeks as needed. The levels of relevant biochemical indexes were detected. The weight of liver was recorded to calculate liver weight index (LWI), and the pathological changes of liver tissues were detected by light and electron microscopy. The levels of AMPK, p-AMPK, mTOR, p-mTOR in rat liver were detected by Western blot.</p><p><strong>Results: </strong>Compared with control group, the levels of LWI, homeostasis model assessment of insulin resistance, fasting blood glucose, alanine transaminase, aspartate transaminase, gamma glutamyl transferase and triglyceride in T2DM group were increased significantly (all <i>P</i><0.05). The liver tissue lesions were more serious and hepatic steatosis grade was higher. The expression of p-AMPK was decreased (<i>P</i><0.05) and the expression of p-mTOR was increased significantly(<i>P</i><0.05). α-lipoic acid could reverse the above-mentioned changes, ameliorate insulin resistance (all <i>P</i><0.05), protect the structure and function of liver, and activate the AMPK/mTOR pathway (<i>P</i><0.05). The protection of α-lipoic acid was weakened by the inhibition of AMPK with Compound C (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>α-lipoic acid could protect the liver of rats with T2DM by activating AMPK/mTOR pathway.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"[α-lipoic acid ameliorates liver injury in rats with type 2 diabetes mellitus <i>via</i> activating AMPK/mTOR pathway].\",\"authors\":\"Xuan Qiu, Lei Yu, Si-Yu Tian, Ya-Jie Chen, Hong-Ling Yan, Kuan-Zhi Liu\",\"doi\":\"10.12047/j.cjap.6312.2022.098\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate the effect of α-lipoic acid in ameliorating liver injury in rats with type 2 diabetes mellitus <i>via</i> activating adenosine 5'-monophosphate-activate protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.</p><p><strong>Methods: </strong>The T2DM rat models were established by feeding with high-fat, high-sucrose diet and intraperitoneal injection of 27.5 mg/(kg·d) streptozotocin. The 32 rats with T2DM were randomly divided into 4 groups: T2DM group, α-lipoic acid group (LA), Compound C group (Comp C, an inhibitor of AMPK) and LA+Comp C group, with 8 rats in each group. Additionally, 8 Sprague-Dawlay (SD) rats without diabetes were set as normal control. The rats received α-lipoic acid at a dosage of 100 mg/(kg·d) or Compound C at a dosage of 20 mg/(kg·d) by intraperitoneal injection for 8 weeks as needed. The levels of relevant biochemical indexes were detected. The weight of liver was recorded to calculate liver weight index (LWI), and the pathological changes of liver tissues were detected by light and electron microscopy. The levels of AMPK, p-AMPK, mTOR, p-mTOR in rat liver were detected by Western blot.</p><p><strong>Results: </strong>Compared with control group, the levels of LWI, homeostasis model assessment of insulin resistance, fasting blood glucose, alanine transaminase, aspartate transaminase, gamma glutamyl transferase and triglyceride in T2DM group were increased significantly (all <i>P</i><0.05). The liver tissue lesions were more serious and hepatic steatosis grade was higher. The expression of p-AMPK was decreased (<i>P</i><0.05) and the expression of p-mTOR was increased significantly(<i>P</i><0.05). α-lipoic acid could reverse the above-mentioned changes, ameliorate insulin resistance (all <i>P</i><0.05), protect the structure and function of liver, and activate the AMPK/mTOR pathway (<i>P</i><0.05). The protection of α-lipoic acid was weakened by the inhibition of AMPK with Compound C (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>α-lipoic acid could protect the liver of rats with T2DM by activating AMPK/mTOR pathway.</p>\",\"PeriodicalId\":23985,\"journal\":{\"name\":\"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.12047/j.cjap.6312.2022.098\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.12047/j.cjap.6312.2022.098","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
[α-lipoic acid ameliorates liver injury in rats with type 2 diabetes mellitus via activating AMPK/mTOR pathway].
Objective: To investigate the effect of α-lipoic acid in ameliorating liver injury in rats with type 2 diabetes mellitus via activating adenosine 5'-monophosphate-activate protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.
Methods: The T2DM rat models were established by feeding with high-fat, high-sucrose diet and intraperitoneal injection of 27.5 mg/(kg·d) streptozotocin. The 32 rats with T2DM were randomly divided into 4 groups: T2DM group, α-lipoic acid group (LA), Compound C group (Comp C, an inhibitor of AMPK) and LA+Comp C group, with 8 rats in each group. Additionally, 8 Sprague-Dawlay (SD) rats without diabetes were set as normal control. The rats received α-lipoic acid at a dosage of 100 mg/(kg·d) or Compound C at a dosage of 20 mg/(kg·d) by intraperitoneal injection for 8 weeks as needed. The levels of relevant biochemical indexes were detected. The weight of liver was recorded to calculate liver weight index (LWI), and the pathological changes of liver tissues were detected by light and electron microscopy. The levels of AMPK, p-AMPK, mTOR, p-mTOR in rat liver were detected by Western blot.
Results: Compared with control group, the levels of LWI, homeostasis model assessment of insulin resistance, fasting blood glucose, alanine transaminase, aspartate transaminase, gamma glutamyl transferase and triglyceride in T2DM group were increased significantly (all P<0.05). The liver tissue lesions were more serious and hepatic steatosis grade was higher. The expression of p-AMPK was decreased (P<0.05) and the expression of p-mTOR was increased significantly(P<0.05). α-lipoic acid could reverse the above-mentioned changes, ameliorate insulin resistance (all P<0.05), protect the structure and function of liver, and activate the AMPK/mTOR pathway (P<0.05). The protection of α-lipoic acid was weakened by the inhibition of AMPK with Compound C (P<0.05).
Conclusion: α-lipoic acid could protect the liver of rats with T2DM by activating AMPK/mTOR pathway.