Environmentally relevant concentrations of clozapine induced lipotoxicity and gut microbiota dysbiosis in Chinese rare minnow (Gobiocypris rarus). (1st October 2021)

• Record Type: Journal Article
• Authors: Xin, Jiajing; Yan, Saihong; Hong, Xiangsheng; Zhang, Huan; Zha, Jinmiao
• Is Part Of: Environmental pollution. Volume 286(2021)
• Publication Date: 2021-10-01
• Subjects: Clozapine -- Lipotoxicity -- Gut microbiota dysbiosis -- Chinese rare minnow; CLZ Clozapine -- HSI Hepatosomatic indices -- K Condition factor -- TG Triglyceride -- T-CHO Total cholesterol -- HDL-C High-density lipoprotein cholesterol -- LDL-C Low-density lipoprotein cholesterol -- SREBP1 sterol regulatory element binding proteins 1 -- SREBP2 sterol regulatory element binding proteins 2 -- FAS fatty acid synthase -- ACC1 Acetyl-CoA carboxylase 1 -- HMGCR 3-Hydroxy-3-Methylglutaryl-CoA Reductase -- LXRα Liver X receptor alpha -- HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 -- DGAT1α Diacylglycerol-acyltransferase 1 alpha -- DGAT1β Diacylglycerol-acyltransferase 1 beta -- DGAT2 Diacylglycerol-acyltransferase 2 -- CYP7A1α Cholesterol 7α-hydroxylase -- FDFT1 farnesyl diphosphate farnesyl transferase 1 -- IDI1 isopentenyl diphosphate isomerase -- PLIN1 perilipin1 -- PLIN2 perilipin2; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.117298
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Clozapine (CLZ) is a neuroactive pharmaceutical that is frequently detected in aquatic environments. Although the cardiotoxicity, developmental toxicity, and neurotoxicity of CLZ in aquatic non-target organisms have been reported, its lipotoxicity and underlying mechanism are unknown. Therefore, in this study, 2-month-old Chinese rare minnows were exposed to 0, 0.1, 1, and 10 μg/L CLZ for 90 days. Overt dyslipidemia was observed after CLZ exposure, whereas the body weights of females significantly increased after CLZ exposure (p < 0.05). In addition, obvious hepatocyte vacuolization and hepatic lipid droplet accumulation were observed at all treatment groups (p < 0.05). The activities of sterol regulatory element binding proteins 1 (SREBP1) and fatty acid synthase (FAS) were significantly upregulated at the 1 and 10 μg/L CLZ treatment groups (p < 0.05). Moreover, evident cell boundary disintegration of the intestinal villi and increasing mucus secretion were observed at all treatment groups (p < 0.05). Furthermore, the diversity of the gut microbiota increased, whereas the relative abundances of Proteobacteria, Firmicutes and Bacteroidetes significantly increased after CLZ exposure (p < 0.05). Furthermore, significantly increased bacterial secondary bile acid biosynthesis activity in Chinese rare minnows was observed after 1 μg/L CLZ exposure (p < 0.05). Therefore, our findings confirmed that CLZ induced lipotoxicity by stimulating SREBP1 and affecting the bacterial secondary bile acid biosynthesis activity in Chinese rare minnows. Graphical abstract: Image 1 Highlights: Clozapine induced lipotoxicity and gut microbiota dysbiosis in Gobiocypris rarus. Clozapine induced lipogenesis by stimulating SREBP1 activity in Gobiocypris rarus. Clozapine increased secondary bile acid biosynthesis in the gut of Gobiocypris rarus. Abstract : Clozapine induced lipotoxicity and gut microbiota dysbiosis in Chinese rare minnow.