Jian Zhou, Sian Xu, Yue Zhu, Xin Li, Ao Wang, Junfang Hu, Li Li, Yan Liu
{"title":"抑制neuropilin-1可改善高脂饮食诱导的肥胖小鼠的非酒精性脂肪性肝病。","authors":"Jian Zhou, Sian Xu, Yue Zhu, Xin Li, Ao Wang, Junfang Hu, Li Li, Yan Liu","doi":"10.23736/S2724-6507.22.03895-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Research findings indicate that neuropilin-1 plays a critical role in lipid metabolism and obesity-associated insulin resistance; on such a basis, the aim of this study was to explore the effects and working mechanism of neuropilin-1 inhibition on the non-alcoholic fatty liver (NAFLD) disease in high-fat-diet (HFD) induced obese mice.</p><p><strong>Methods: </strong>Firstly, the pcDNA3.1-NRP-1 recombinant plasmid containing neuropilin-1 (NRP1) gene and NRP1 RNA interference plasmid shRNA-NRP1 were successfully constructed. A total of 36 C57BL/6 mice were randomly assigned to 6 groups, blank group, control group, pcDNA3.1 injection group, pcDNA3.1-NRP-1 injection group, pGenesil-1.1 injection group and shRNA-NRP1 injection group. Expression of phospho-PI3K, phospho-AKT, phospho-mTOR and neuropilin-1 in liver was measured as well as body and liver weight, blood glucose, serum transaminases and lipid levels of the mice.</p><p><strong>Results: </strong>The weight and liver mass of HFD fed mice injected with pcDNA3.1-NRP-1 were significantly higher than those from the control group, but their body weight and liver mass decreased significantly after shRNA-NRP1 injection. The results also showed that neuropilin-1 expression can significantly influence the severity of hepatic steatosis in HFD fed mice, decreased serum FPG, LDL, AST, ALT levels and the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA. In addition, the Neuropilin-1 expression will also influence the p-PI3K, p-AKT and p-mTOR in mice.</p><p><strong>Conclusions: </strong>This study concluded that the inhibition of neuropilin-1 could improve NAFLD disease by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the PI3K/AKT/mTOR signaling pathway.</p>","PeriodicalId":18690,"journal":{"name":"Minerva endocrinology","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhibition of neuropilin-1 improves non-alcoholic fatty liver disease in high-fat-diet induced obese mouse.\",\"authors\":\"Jian Zhou, Sian Xu, Yue Zhu, Xin Li, Ao Wang, Junfang Hu, Li Li, Yan Liu\",\"doi\":\"10.23736/S2724-6507.22.03895-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Research findings indicate that neuropilin-1 plays a critical role in lipid metabolism and obesity-associated insulin resistance; on such a basis, the aim of this study was to explore the effects and working mechanism of neuropilin-1 inhibition on the non-alcoholic fatty liver (NAFLD) disease in high-fat-diet (HFD) induced obese mice.</p><p><strong>Methods: </strong>Firstly, the pcDNA3.1-NRP-1 recombinant plasmid containing neuropilin-1 (NRP1) gene and NRP1 RNA interference plasmid shRNA-NRP1 were successfully constructed. A total of 36 C57BL/6 mice were randomly assigned to 6 groups, blank group, control group, pcDNA3.1 injection group, pcDNA3.1-NRP-1 injection group, pGenesil-1.1 injection group and shRNA-NRP1 injection group. Expression of phospho-PI3K, phospho-AKT, phospho-mTOR and neuropilin-1 in liver was measured as well as body and liver weight, blood glucose, serum transaminases and lipid levels of the mice.</p><p><strong>Results: </strong>The weight and liver mass of HFD fed mice injected with pcDNA3.1-NRP-1 were significantly higher than those from the control group, but their body weight and liver mass decreased significantly after shRNA-NRP1 injection. The results also showed that neuropilin-1 expression can significantly influence the severity of hepatic steatosis in HFD fed mice, decreased serum FPG, LDL, AST, ALT levels and the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA. In addition, the Neuropilin-1 expression will also influence the p-PI3K, p-AKT and p-mTOR in mice.</p><p><strong>Conclusions: </strong>This study concluded that the inhibition of neuropilin-1 could improve NAFLD disease by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the PI3K/AKT/mTOR signaling pathway.</p>\",\"PeriodicalId\":18690,\"journal\":{\"name\":\"Minerva endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Minerva endocrinology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.23736/S2724-6507.22.03895-7\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Minerva endocrinology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.23736/S2724-6507.22.03895-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Inhibition of neuropilin-1 improves non-alcoholic fatty liver disease in high-fat-diet induced obese mouse.
Background: Research findings indicate that neuropilin-1 plays a critical role in lipid metabolism and obesity-associated insulin resistance; on such a basis, the aim of this study was to explore the effects and working mechanism of neuropilin-1 inhibition on the non-alcoholic fatty liver (NAFLD) disease in high-fat-diet (HFD) induced obese mice.
Methods: Firstly, the pcDNA3.1-NRP-1 recombinant plasmid containing neuropilin-1 (NRP1) gene and NRP1 RNA interference plasmid shRNA-NRP1 were successfully constructed. A total of 36 C57BL/6 mice were randomly assigned to 6 groups, blank group, control group, pcDNA3.1 injection group, pcDNA3.1-NRP-1 injection group, pGenesil-1.1 injection group and shRNA-NRP1 injection group. Expression of phospho-PI3K, phospho-AKT, phospho-mTOR and neuropilin-1 in liver was measured as well as body and liver weight, blood glucose, serum transaminases and lipid levels of the mice.
Results: The weight and liver mass of HFD fed mice injected with pcDNA3.1-NRP-1 were significantly higher than those from the control group, but their body weight and liver mass decreased significantly after shRNA-NRP1 injection. The results also showed that neuropilin-1 expression can significantly influence the severity of hepatic steatosis in HFD fed mice, decreased serum FPG, LDL, AST, ALT levels and the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA. In addition, the Neuropilin-1 expression will also influence the p-PI3K, p-AKT and p-mTOR in mice.
Conclusions: This study concluded that the inhibition of neuropilin-1 could improve NAFLD disease by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the PI3K/AKT/mTOR signaling pathway.