Inhibition of Neuropilin-1 Improves Non-Alcoholic Fatty Liver Disease via PI3K/AKT/Mtor Signaling in High-Fat-Diet induced Obese Mouse

Background: Research findings indicate Neuropilin-1 plays a critical role in lipid metabolism and obesity-associated insulin resistance, on such a basis, this study aims to explore the effects and working mechanism of Neuropilin-1 inhibition on the non-alcoholic fatty liver disease in high-fat-diet induced obese mice. Methods: Firstly, the pcDNA3.1-NRP-1 recombinant plasmid containing Neuropilin-1 gene and the Neuropilin-1 gene 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 high-fat-diet 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 high-fat-diet fed mice, decreased serum FPG, LDL, AST, ALT levels and the expression of TNF-α, 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 Non-alcoholic fatty liver disease by decreasing body weight and reduce inflammation in high-fat-diet induced obese mice by modulating the PI3K/AKT/mTOR signaling pathway.