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Int J Biol Sci 2024; 20(6):2027-2043. doi:10.7150/ijbs.86465 This issue Cite

Research Paper

The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD

Yue Jiang1*, Pengcheng Luo2*, Yu Cao1, Dewei Peng1, Shengqi Huo1, Junyi Guo1, Moran Wang1, Wei Shi1, Cuntai Zhang2, Sheng Li1, Li Lin1✉, Jiagao Lv1✉

1. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2. Departments of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
*These authors have contributed equally to this work and share first authorship.

✉ Corresponding authors: Li Lin, Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Email address: linlitjmu.edu.cn. Jiagao Lv, Div More

Citation:
Jiang Y, Luo P, Cao Y, Peng D, Huo S, Guo J, Wang M, Shi W, Zhang C, Li S, Lin L, Lv J. The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. Int J Biol Sci 2024; 20(6):2027-2043. doi:10.7150/ijbs.86465. https://www.ijbs.com/v20p2027.htm
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Abstract

Graphic abstract

Metabolic-associated fatty liver disease (MAFLD) is a globally prevalent chronic hepatic disease. Previous studies have indicated that the activation of the signal transducer and activator of transcription3 (STAT3) plays a vital role in MAFLD progression at the very beginning. However, the specific association between STAT3 and abnormal hepatic metabolism remains unclear. In this study, activated inflammation was observed to induce abnormal glucolipid metabolic disorders in the hepatic tissues of high-fat diet (HFD)-fed ApoE-/- mice. Furthermore, we found that the activation of STAT3 induced by HFD might function as a transcriptional factor to suppress the expression of VAV3, which might participate in intracellular glucolipid metabolism and the regulation of glucose transporter 4 (GLUT4) storage vesicle traffic in the development of MAFLD both in vitro and in vivo. We verified that VAV3 deficiency could retard the GLUT4 membrane translocation and impair the glucose homeostasis. Additionally, VAV3 participates in cholesterol metabolism in hepatocytes, eventually resulting in the accumulation of intracellular cholesterol. Moreover, rAAV8-TBG-VAV3 was conducted to restore the expression of VAV3 in HFD-fed ApoE-/- mice. VAV3 overexpression was observed to improve glucose homeostasis as well as attenuate hepatic cholesterol accumulation in vivo. In conclusion, the STAT3/VAV3 signaling pathway might play a significant role in MAFLD by regulating glucose and cholesterol metabolism, and VAV3 might be a potential therapeutic strategy which could consequently ameliorate MAFLD.

Keywords: MAFLD, glucolipid metabolism, STAT3, VAV3, GLUT4

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APA
Jiang, Y., Luo, P., Cao, Y., Peng, D., Huo, S., Guo, J., Wang, M., Shi, W., Zhang, C., Li, S., Lin, L., Lv, J. (2024). The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. International Journal of Biological Sciences, 20(6), 2027-2043. https://doi.org/10.7150/ijbs.86465.

ACS
Jiang, Y.; Luo, P.; Cao, Y.; Peng, D.; Huo, S.; Guo, J.; Wang, M.; Shi, W.; Zhang, C.; Li, S.; Lin, L.; Lv, J. The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. Int. J. Biol. Sci. 2024, 20 (6), 2027-2043. DOI: 10.7150/ijbs.86465.

NLM
Jiang Y, Luo P, Cao Y, Peng D, Huo S, Guo J, Wang M, Shi W, Zhang C, Li S, Lin L, Lv J. The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. Int J Biol Sci 2024; 20(6):2027-2043. doi:10.7150/ijbs.86465. https://www.ijbs.com/v20p2027.htm

CSE
Jiang Y, Luo P, Cao Y, Peng D, Huo S, Guo J, Wang M, Shi W, Zhang C, Li S, Lin L, Lv J. 2024. The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. Int J Biol Sci. 20(6):2027-2043.

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