Reducing VEGFB accelerates NAFLD and insulin resistance in mice via inhibiting AMPK signaling pathway

Objective: Vascular endothelial growth factor B (VEGFB) was regarded to improve lipid metabolism and reduce obesity-related hyperlipidemia. Whether VEGFB participates in lipid metabolism in nonalcoholic fatty liver disease (NAFLD) has not been clear yet. This study investigated the involvement of VEGFB in lipid metabolism and insulin resistance via the AMPK signaling pathway in NAFLD. Methods: : We constructed the animal and cell model of NAFLD after VEGFB gene knockout to detect liver damage and metabolism in NAFLD. Bioinformatics analysis of VEGFB and the AMPK signaling pathway relative genes to verify the differential proteins. And mRNA levels of NAFLD fatty acid metabolism-related genes were detected. Results: : Our study found that after high-fat diet (HFD), body fat content, serum lipoprotein and NAFLD scores of VEGFB knockout mice increased, and insulin resistance was distinct. The phosphorylation level of proteins in the AMPK / ACC / CPT1 was descended after reducing VEGFB, so as to inhibit the oxidation of fatty acids in hepatocytes mitochondria. Conclusion: Consequently, reducing VEGFB also increased the expression level of proteins in the AMPK / SREBP1 / Scd1 pathway and resulted in endoplasmic reticulum lipid synthesis.