Wen Liu, Qiyu He, Caiyu Yue, Tong Xu, Xiaoming Hang
{"title":"脱氯剂对雄性小鼠肝脏病理学、新陈代谢健康和肠道微生物群的影响","authors":"Wen Liu, Qiyu He, Caiyu Yue, Tong Xu, Xiaoming Hang","doi":"10.1016/j.scitotenv.2024.177532","DOIUrl":null,"url":null,"abstract":"<p><p>Dechlorane plus (DP), a widely used flame retardant, was added to Annex A of the Stockholm Convention on Persistent Organic Pollutants in 2023. This study aimed to investigate the effects of DP on glucose and lipid metabolism by orally exposing eight-week-old male mice to environmentally relevant concentrations of DP (0.5, 1, and 5 mg/kg/day) for six weeks. The in vivo effects of DP on liver histomorphology, glucose and lipid metabolism, intestinal microbiota, and the associated molecular mechanisms were assessed. Pathological examination revealed that exposure to 1 and 5 mg/kg/day DP induced hepatic damage, characterized by structural disarray of the hepatic cords and vacuolar degeneration of liver cells, while 0.5 and 1 mg/kg/day DP exposure led to significant triglycerides (TG) accumulation in the liver. Metabolite analysis showed a marked increase in hepatic pyruvate, glycogen, and TG in mice exposed to 0.5 and 1 mg/kg/day DP, while 5 mg/kg/day exposure resulted in elevated glycogen levels and reduced pyruvate and glucose concentrations. The underlying mechanisms involved the transcriptional regulation of key enzymes related to glucose and lipid metabolism, as well as the activation of the PI3K/AKT pathway. Exposure to 5 mg/kg/day DP upregulated genes associated with glycogenesis (GK), glycolysis (HK1 and PK), and fatty acid synthesis (SREBP1, FAS, and ACC1), while downregulating genes involved in gluconeogenesis (PCK1) and fatty acid β-oxidation (CPT1 and PPARA). The activated PI3K/AKT pathway regulated key proteins (GLUT4, GSK3β, and FoxO1), playing distinct roles in glucose and lipid metabolism. High-throughput 16S rDNA sequencing revealed that 5 mg/kg/day DP exposure altered the composition and diversity of intestinal microbiota, reducing the relative abundance of beneficial probiotics at both the phylum and genus levels. These findings offer new insights into the complex mechanisms through which DP affects glucose and lipid metabolism in mammals, contributing to a more comprehensive evaluation of its toxicity.</p>","PeriodicalId":422,"journal":{"name":"Science of the Total Environment","volume":" ","pages":"177532"},"PeriodicalIF":8.2000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of dechlorane plus on hepatic pathology, metabolic health and gut microbiota in male mice.\",\"authors\":\"Wen Liu, Qiyu He, Caiyu Yue, Tong Xu, Xiaoming Hang\",\"doi\":\"10.1016/j.scitotenv.2024.177532\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Dechlorane plus (DP), a widely used flame retardant, was added to Annex A of the Stockholm Convention on Persistent Organic Pollutants in 2023. This study aimed to investigate the effects of DP on glucose and lipid metabolism by orally exposing eight-week-old male mice to environmentally relevant concentrations of DP (0.5, 1, and 5 mg/kg/day) for six weeks. The in vivo effects of DP on liver histomorphology, glucose and lipid metabolism, intestinal microbiota, and the associated molecular mechanisms were assessed. Pathological examination revealed that exposure to 1 and 5 mg/kg/day DP induced hepatic damage, characterized by structural disarray of the hepatic cords and vacuolar degeneration of liver cells, while 0.5 and 1 mg/kg/day DP exposure led to significant triglycerides (TG) accumulation in the liver. Metabolite analysis showed a marked increase in hepatic pyruvate, glycogen, and TG in mice exposed to 0.5 and 1 mg/kg/day DP, while 5 mg/kg/day exposure resulted in elevated glycogen levels and reduced pyruvate and glucose concentrations. The underlying mechanisms involved the transcriptional regulation of key enzymes related to glucose and lipid metabolism, as well as the activation of the PI3K/AKT pathway. Exposure to 5 mg/kg/day DP upregulated genes associated with glycogenesis (GK), glycolysis (HK1 and PK), and fatty acid synthesis (SREBP1, FAS, and ACC1), while downregulating genes involved in gluconeogenesis (PCK1) and fatty acid β-oxidation (CPT1 and PPARA). The activated PI3K/AKT pathway regulated key proteins (GLUT4, GSK3β, and FoxO1), playing distinct roles in glucose and lipid metabolism. High-throughput 16S rDNA sequencing revealed that 5 mg/kg/day DP exposure altered the composition and diversity of intestinal microbiota, reducing the relative abundance of beneficial probiotics at both the phylum and genus levels. These findings offer new insights into the complex mechanisms through which DP affects glucose and lipid metabolism in mammals, contributing to a more comprehensive evaluation of its toxicity.</p>\",\"PeriodicalId\":422,\"journal\":{\"name\":\"Science of the Total Environment\",\"volume\":\" \",\"pages\":\"177532\"},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2024-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science of the Total Environment\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1016/j.scitotenv.2024.177532\",\"RegionNum\":1,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science of the Total Environment","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1016/j.scitotenv.2024.177532","RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Effects of dechlorane plus on hepatic pathology, metabolic health and gut microbiota in male mice.
Dechlorane plus (DP), a widely used flame retardant, was added to Annex A of the Stockholm Convention on Persistent Organic Pollutants in 2023. This study aimed to investigate the effects of DP on glucose and lipid metabolism by orally exposing eight-week-old male mice to environmentally relevant concentrations of DP (0.5, 1, and 5 mg/kg/day) for six weeks. The in vivo effects of DP on liver histomorphology, glucose and lipid metabolism, intestinal microbiota, and the associated molecular mechanisms were assessed. Pathological examination revealed that exposure to 1 and 5 mg/kg/day DP induced hepatic damage, characterized by structural disarray of the hepatic cords and vacuolar degeneration of liver cells, while 0.5 and 1 mg/kg/day DP exposure led to significant triglycerides (TG) accumulation in the liver. Metabolite analysis showed a marked increase in hepatic pyruvate, glycogen, and TG in mice exposed to 0.5 and 1 mg/kg/day DP, while 5 mg/kg/day exposure resulted in elevated glycogen levels and reduced pyruvate and glucose concentrations. The underlying mechanisms involved the transcriptional regulation of key enzymes related to glucose and lipid metabolism, as well as the activation of the PI3K/AKT pathway. Exposure to 5 mg/kg/day DP upregulated genes associated with glycogenesis (GK), glycolysis (HK1 and PK), and fatty acid synthesis (SREBP1, FAS, and ACC1), while downregulating genes involved in gluconeogenesis (PCK1) and fatty acid β-oxidation (CPT1 and PPARA). The activated PI3K/AKT pathway regulated key proteins (GLUT4, GSK3β, and FoxO1), playing distinct roles in glucose and lipid metabolism. High-throughput 16S rDNA sequencing revealed that 5 mg/kg/day DP exposure altered the composition and diversity of intestinal microbiota, reducing the relative abundance of beneficial probiotics at both the phylum and genus levels. These findings offer new insights into the complex mechanisms through which DP affects glucose and lipid metabolism in mammals, contributing to a more comprehensive evaluation of its toxicity.
期刊介绍:
The Science of the Total Environment is an international journal dedicated to scientific research on the environment and its interaction with humanity. It covers a wide range of disciplines and seeks to publish innovative, hypothesis-driven, and impactful research that explores the entire environment, including the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere.
The journal's updated Aims & Scope emphasizes the importance of interdisciplinary environmental research with broad impact. Priority is given to studies that advance fundamental understanding and explore the interconnectedness of multiple environmental spheres. Field studies are preferred, while laboratory experiments must demonstrate significant methodological advancements or mechanistic insights with direct relevance to the environment.