Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1

Luo,Xu; Li,Rong-Rong; Li,Yu-Qi; Yu,Han-Pu; Yu,Hai-Ning; Jiang,Wen-Guo; Li,Ya-Na

doi:10.3892/mmr.2022.12801

Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1

Authors:
- Xu Luo
- Rong-Rong Li
- Yu-Qi Li
- Han-Pu Yu
- Hai-Ning Yu
- Wen-Guo Jiang
- Ya-Na Li
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Affiliations: Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Clinical Medicine, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Stomatology Medicine, School of Oral Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: July 26, 2022 https://doi.org/10.3892/mmr.2022.12801
Article Number: 285
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In recent years, studies have demonstrated that vascular endothelial growth factor B (VEGFB) can affect the metabolism of fatty acids and glucose, and it is expected to become a target for the diagnosis and treatment of metabolic diseases such as obesity and diabetes. At present, the specific mechanism that VEGFB regulates lipid and glucose metabolism balance is not completely understood. The present study used systemic VEGFB gene‑knockout mice to investigate the effects of downregulation of the VEGFB gene on lipid metabolism and insulin secretion, and to explore the mechanism of the VEGFB pathway involved in the regulation of glucose and lipid metabolism. The morphological changes in the liver and pancreas of mice after VEGFB gene deletion were observed under a light microscope and a scanning electron microscope, and the effects of VEGFB gene deletion on lipid metabolism and blood glucose balance were detected by a serological technique. The detection indexes included total cholesterol (TC), triglyceride (TG), low‑density lipoprotein cholesterol (LDL‑C) and high‑density lipoprotein cholesterol. Simultaneously, fasting blood glucose, glycosylated hemoglobin A1c (HbA1c), fasting insulin and glucagon were measured. Insulin sensitivity was assessed by using the insulin tolerance tests and glucose tolerance tests, and function of β‑cell islets was evaluated by using the insulin resistance index (HOMA‑IR) and pancreatic β‑cell secretion index (HOMA‑β). Τhe protein expression changes of vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) in mouse islets were detected by western blotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) after the VEGFB gene was knocked down to analyze the mechanism of VEGFB that may be involved in glucose and lipid metabolism. It was observed that after VEGFB was knocked down, mouse hepatocytes exhibited steatosis and increased secretory vesicles in islet cells. The lipid metabolism indexes such as TG, TC and LDL increased significantly; however, the levels of FBS, postprandial blood glucose and HbA1c decreased, whereas the glucose tolerance increased. Serum insulin secretion increased and HOMA‑IR decreased since VEGFB was knocked down. Western blotting and RT‑qPCR results revealed that the expression levels of VEGFR1 and neuropilin‑1 decreased after the VEGFB gene was knocked down, while the expression levels of VEGFA and VEGFR2 increased. The absence of VEGFB may be involved in the regulation of glucose and lipid metabolism in mice by activating the VEGFA/VEGFR2 signaling pathway. VEGFB is expected to become a new target for the treatment of metabolic diseases such as obesity and diabetes. At present, the mechanism of VEGFB involved in regulating lipid metabolism and glucose metabolism is not completely clear. It was identified that downregulating VEGFB improved lipid metabolism and insulin resistance. The role of VEGFB/VEGFR1 pathway and other family members in regulating glucose and lipid metabolism was detected, which provided a theoretical and experimental basis for VEGFB to affect the regulation of glucose and lipid metabolism balance.

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