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降低 VEGFB 可通过抑制 AMPK 信号通路加速小鼠的非酒精性脂肪性肝病和胰岛素抵抗。

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

机构信息

Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai, 264000, Shandong, China.

Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai, 264000, Shandong, China.

出版信息

J Transl Med. 2022 Jul 30;20(1):341. doi: 10.1186/s12967-022-03540-2.

DOI:10.1186/s12967-022-03540-2
PMID:35907871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9338666/
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.

摘要

目的

血管内皮生长因子 B（VEGFB）被认为可以改善脂质代谢，减轻肥胖相关的高脂血症。然而，VEGFB 是否参与非酒精性脂肪性肝病（NAFLD）中的脂质代谢尚不清楚。本研究通过 AMPK 信号通路探讨了 VEGFB 在 NAFLD 中脂质代谢和胰岛素抵抗中的作用。

方法

我们构建了 VEGFB 基因敲除的 NAFLD 动物和细胞模型，以检测 NAFLD 中的肝损伤和代谢情况。对 VEGFB 和 AMPK 信号通路相关基因进行生物信息学分析，以验证差异蛋白。并检测了 NAFLD 脂肪酸代谢相关基因的 mRNA 水平。

结果

在高脂喂养的全身性 VEGFB 敲除小鼠中，体脂肪、血清脂蛋白、NAFLD 评分和胰岛素抵抗增加。动物和细胞实验表明，CaMKK2 和 AMPK 的磷酸化蛋白表达降低，AMPK/ACC/CPT1 信号通路相关蛋白表达降低，相应的靶基因 CPT1α 和 Lcad 减少，导致肝细胞线粒体中的脂肪酸氧化减少；AMPK/SREBP1/Scd1 信号通路相关蛋白的表达增加，ACC1 和 FAS 相应增加，导致内质网中的脂质合成增加。

结论

VEGFB 可以通过 AMPK 信号通路参与 NAFLD 的脂质代谢和胰岛素抵抗。

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