Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social e...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522001511 |
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| author | Ting Ding Siping Chen Wenchang Xiao Zhen Liu Jun Tu Yongjie Yu Bizhen Dong Wenping Chen Yong Zeng |
| author_facet | Ting Ding Siping Chen Wenchang Xiao Zhen Liu Jun Tu Yongjie Yu Bizhen Dong Wenping Chen Yong Zeng |
| author_sort | Ting Ding |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of NAFLD. Therefore, it is important to further investigate the pathogenesis of NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a STEAP family protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver ischemia-reperfusion injury, hepatocellular carcinoma, myocardial hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in NAFLD. Deletion of STEAP3 inhibits the development of NAFLD in vivo and in vitro, whereas its overexpression promotes palmitic acid/oleic acid stimulation-induced lipid deposition in hepatocytes. Mechanistically, it interacts with transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology. |
| first_indexed | 2024-04-10T20:33:42Z |
| format | Article |
| id | doaj.art-3336b13823304932950b003bedcee3fb |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-10T20:33:42Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-3336b13823304932950b003bedcee3fb2023-01-25T04:14:41ZengElsevierJournal of Lipid Research0022-22752023-01-01641100318Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and SteatosisTing Ding0Siping Chen1Wenchang Xiao2Zhen Liu3Jun Tu4Yongjie Yu5Bizhen Dong6Wenping Chen7Yong Zeng8Department of Endocrinology, Huanggang Central Hospital, Huanggang, ChinaDepartment of Endocrinology, Huanggang Central Hospital, Huanggang, ChinaDepartment of Cardiovascular Surgery, Huanggang Central Hospital, Huanggang, China; Huanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHuanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, ChinaHuanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, ChinaHuanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, ChinaDepartment of Endocrinology, Huanggang Central Hospital, Huanggang, China; For correspondence: Wenping Chen; Yong ZengDepartment of Stomatology, Huanggang Central Hospital, Huanggang, China; For correspondence: Wenping Chen; Yong ZengNonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of NAFLD. Therefore, it is important to further investigate the pathogenesis of NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a STEAP family protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver ischemia-reperfusion injury, hepatocellular carcinoma, myocardial hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in NAFLD. Deletion of STEAP3 inhibits the development of NAFLD in vivo and in vitro, whereas its overexpression promotes palmitic acid/oleic acid stimulation-induced lipid deposition in hepatocytes. Mechanistically, it interacts with transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology.http://www.sciencedirect.com/science/article/pii/S0022227522001511STEAP3metalloreductaseNAFLDglucose metabolism disorderlipid depositionhepatic steatosis |
| spellingShingle | Ting Ding Siping Chen Wenchang Xiao Zhen Liu Jun Tu Yongjie Yu Bizhen Dong Wenping Chen Yong Zeng Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis Journal of Lipid Research STEAP3 metalloreductase NAFLD glucose metabolism disorder lipid deposition hepatic steatosis |
| title | Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis |
| title_full | Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis |
| title_fullStr | Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis |
| title_full_unstemmed | Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis |
| title_short | Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis |
| title_sort | six transmembrane epithelial antigen of prostate 3 promotes hepatic insulin resistance and steatosis |
| topic | STEAP3 metalloreductase NAFLD glucose metabolism disorder lipid deposition hepatic steatosis |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522001511 |
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