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ORIGINAL ARTICLE Open access
Minerva Endocrinology 2023 June;48(2):194-205
DOI: 10.23736/S2724-6507.22.03895-7
Copyright © 2022 THE AUTHORS
This is an open access article distributed under the terms of the CC BY-NC 4.0 license which allows users to distribute, remix, adapt and build upon the manuscript, as long as this is not done for commercial purposes, the user gives appropriate credits to the original author(s) and the source (with a link to the formal publication through the relevant DOI), provides a link to the license and indicates if changes were made.
language: English
Inhibition of neuropilin-1 improves non-alcoholic fatty liver disease in high-fat-diet induced obese mouse
Jian ZHOU 1, Sian XU 2, Yue ZHU 2, Xin LI 2, Ao WANG 1, Junfang HU 3, Li LI 4, Yan LIU 2 ✉
1 Department of Infectious Disease, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China; 2 Biological Cell Therapy Research Center, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China; 3 Department of Pharmacy, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China; 4 Department of Pathology, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China
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.
KEY WORDS: Neuropilin-1; Non-alcoholic fatty liver disease; Obesity; Inflammation; Phosphatidylinositol 3-kinase; TOR serine-threonine kinases