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Journal of Translational Medicine

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Open Access 01-12-2022 | Insulins | Research

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

Authors: Rongrong Li, Yuqi Li, Xueling Yang, Yaorui Hu, Haining Yu, Yana Li

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

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

After the systemic VEGFB knockout mice were fed with high fat, the body fat, serum lipoprotein, NAFLD score, and insulin resistance were increased. Animal and cell experiments showed that the expression levels of phosphorylated proteins of CaMKK2 and AMPK decreased, the expression of proteins related to AMPK/ACC/CPT1 signaling pathway decreased, and the target genes CPT1α and Lcad decreased accordingly, reducing fatty acid oxidation in hepatocyte mitochondria; The expression of AMPK/SREBP1/Scd1 signaling pathway relative proteins increased, ACC1 and FAS increased correspondingly, which increased lipid synthesis in the endoplasmic reticulum.

Conclusion

VEGFB can participate in lipid metabolism and insulin resistance of NAFLD through the AMPK signaling pathway.

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Title: Reducing VEGFB accelerates NAFLD and insulin resistance in mice via inhibiting AMPK signaling pathway
Authors: Rongrong Li
Yuqi Li
Xueling Yang
Yaorui Hu
Haining Yu
Yana Li
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Insulins
Insulins
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03540-2

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