ORIGINAL ARTICLE   Open access

Minerva Endocrinology 2023 June;48(2):194-205

DOI: 10.23736/S2724-6507.22.03895-7

Copyright © 2022 THE AUTHORS

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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