{"title":"Evaluation of the role of hepatic Gstm4 in diet-induced obesity and dyslipidemia","authors":"Liwei Hu, Delong Yuan, Qihan Zhu, Mengyue Wu, Meng Tie, Shaoxuan Song, Yali Chen, Yunzhi Yang, Anyuan He","doi":"10.1016/j.bbrc.2024.150920","DOIUrl":null,"url":null,"abstract":"<div><div>Obesity and its related diseases continue to rise worldwide, necessitating further investigation to develop new therapeutic strategies. The dysregulation of redox homeostasis is tightly associated with metabolic diseases. Glutathione, an antioxidant, acts as a cofactor for antioxidant and detoxification enzymes such as glutathione S-transferases (GSTs)—a superfamily including Gstm4. So far, the physiological role of Gstm4 remains largely unknown. Human genetics is a powerful tool to discover novel therapeutic targets for metabolic diseases. The single nucleotide polymorphism rs650985, located within the sixth intron of the human gene Gstm4, was associated with plasma lipids, indicating that targeting Gstm4 might intervene in the progression of dyslipidemia. Furthermore, we found that Gstm4 is highly expressed in the liver and enriched in hepatocytes—the parenchymal cells of the liver. We established the mouse model with the hepatic deletion of Gstm4 and found that this mouse model did not present altered body weight, serum lipid profile, or liver fat content in the context of chow or high-fat high cholesterol diet feeding, indicating that hepatic Gstm4 is dispensable for diet-induced obesity and dyslipidemia. Further analysis revealed that hepatic deletion of Gstm4 upregulates the level of protein but not mRNA of Npc1l1—a critical protein mediating cholesterol uptake, suggesting that there might be a link between Gstm4 and lipid metabolic diseases in certain contexts.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical and biophysical research communications","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006291X24014566","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Obesity and its related diseases continue to rise worldwide, necessitating further investigation to develop new therapeutic strategies. The dysregulation of redox homeostasis is tightly associated with metabolic diseases. Glutathione, an antioxidant, acts as a cofactor for antioxidant and detoxification enzymes such as glutathione S-transferases (GSTs)—a superfamily including Gstm4. So far, the physiological role of Gstm4 remains largely unknown. Human genetics is a powerful tool to discover novel therapeutic targets for metabolic diseases. The single nucleotide polymorphism rs650985, located within the sixth intron of the human gene Gstm4, was associated with plasma lipids, indicating that targeting Gstm4 might intervene in the progression of dyslipidemia. Furthermore, we found that Gstm4 is highly expressed in the liver and enriched in hepatocytes—the parenchymal cells of the liver. We established the mouse model with the hepatic deletion of Gstm4 and found that this mouse model did not present altered body weight, serum lipid profile, or liver fat content in the context of chow or high-fat high cholesterol diet feeding, indicating that hepatic Gstm4 is dispensable for diet-induced obesity and dyslipidemia. Further analysis revealed that hepatic deletion of Gstm4 upregulates the level of protein but not mRNA of Npc1l1—a critical protein mediating cholesterol uptake, suggesting that there might be a link between Gstm4 and lipid metabolic diseases in certain contexts.
期刊介绍:
Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology
; molecular biology; neurobiology; plant biology and proteomics