دورية أكاديمية
Chlormequat chloride induces hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.
| العنوان: | Chlormequat chloride induces hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition. |
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| المؤلفون: | Kang C; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Xiao Q; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Wang X; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Guo W; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Zhang H; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Yuan L; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Zhao Z; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China., Hao W; Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address: whao@bjmu.edu.cn. |
| المصدر: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2024 Aug; Vol. 190, pp. 114790. Date of Electronic Publication: 2024 Jun 06. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 8207483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6351 (Electronic) Linking ISSN: 02786915 NLM ISO Abbreviation: Food Chem Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Exeter : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1982- |
| مواضيع طبية MeSH: | TOR Serine-Threonine Kinases*/metabolism , Fatty Liver*/chemically induced , Fatty Liver*/metabolism , Lipogenesis*/drug effects , AMP-Activated Protein Kinases*/metabolism , Sterol Regulatory Element Binding Protein 1*/metabolism , Sterol Regulatory Element Binding Protein 1*/genetics , Chlormequat*/toxicity, Animals ; Male ; Humans ; Hep G2 Cells ; Rats ; Rats, Sprague-Dawley ; Liver/drug effects ; Liver/metabolism |
| مستخلص: | Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo, male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21-60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro, HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 μg/mL) for 24 h. And the results showed that CCC above 120 μg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: AMP-Activated protein kinase; Chlormequat chloride; Hepatic steatosis; Peri-puberty; Rat |
| المشرفين على المادة: | EC 2.7.11.1 (TOR Serine-Threonine Kinases) EC 2.7.11.31 (AMP-Activated Protein Kinases) 0 (Sterol Regulatory Element Binding Protein 1) 8SUZ1123XX (Chlormequat) EC 2.7.1.1 (mTOR protein, rat) 0 (Srebf1 protein, rat) |
| تواريخ الأحداث: | Date Created: 20240607 Date Completed: 20240711 Latest Revision: 20240711 |
| رمز التحديث: | 20240712 |
| DOI: | 10.1016/j.fct.2024.114790 |
| PMID: | 38849044 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-6351 |
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| DOI: | 10.1016/j.fct.2024.114790 |