Inhibition of neuropilin-1 improves non-alcoholic fatty liver disease in high-fat-diet induced obese mouse.

Abstract

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.

• Authors: Jian Zhou, Sian Xu, Yue Zhu, Xin Li, Ao Wang, Junfang Hu, Li Li, Yan Liu
• Journal: Minerva endocrinology (Minerva Endocrinol (Torino)) Vol. 48 Issue 2 Pg. 194-205 (Jun 2023) ISSN: 2724-6116 [Electronic] Italy
• PMID: 36285747 (Publication Type: Journal Article)

Chemical References

• Neuropilin-1
• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• TOR Serine-Threonine Kinases

Topics

• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (etiology, metabolism)
• Mice, Obese
• Neuropilin-1 (genetics)
• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Mice, Inbred C57BL
• Diet, High-Fat (adverse effects)
• Obesity
• TOR Serine-Threonine Kinases