https://scholars.lib.ntu.edu.tw/handle/123456789/605990
標題: | Clozapine worsens glucose intolerance, nonalcoholic fatty liver disease, kidney damage and retinal injury and increases renal reactive oxygen species production and chromium loss in obese mice | 作者: | Chang G.-R Liu H.-Y WEI-CHENG YANG Wang C.-M Wu C.-F Lin J.-W Lin W.-L Wang Y.-C Lin T.-C Liao H.-J Hou P.-H Chan C.-H Lin C.-F. |
關鍵字: | Chromium;Clozapine;Fatty liver disease;Glucose intolerance;Obesity;Reactive oxygen species;Renal damage;Retinal injury;adiponectin;alanine aminotransferase;antioxidant;aspartate aminotransferase;biological marker;catalase;chromium;clozapine;creatinine;fatty acid binding protein 4;fatty acid synthase;glucose;glucose transporter 4;glutathione peroxidase;immunoglobulin enhancer binding protein;inducible nitric oxide synthase;insulin;interleukin 1;messenger RNA;protein kinase B;protein PNPLA3;reactive oxygen metabolite;sterol regulatory element binding protein 1;superoxide dismutase;triacylglycerol;unclassified drug;FABP4 protein, human;fatty acid binding protein;NOS2 protein, human;SREBF1 protein, human;alanine aminotransferase blood level;animal experiment;animal model;animal tissue;Article;aspartate aminotransferase blood level;body weight gain;controlled study;creatinine blood level;diabetes mellitus;disease exacerbation;epididymis fat;food intake;glucose homeostasis;glucose intolerance;hyperglycemia;insulin blood level;insulin resistance;insulin sensitivity;kidney disease;kidney injury;lipid diet;lipid liver level;liver function;liver injury;male;morphometry;mouse;mRNA expression level;nonalcoholic fatty liver;nonhuman;obesity;protein expression level;protein phosphorylation;real time polymerase chain reaction;regulatory mechanism;retina cell;retina injury;retinal thickness;retinopathy;retroperitoneal fat pad;signal transduction;thickness;triacylglycerol blood level;urea nitrogen blood level;urinary excretion;adipocyte;animal;complication;disease model;fluorescent antibody technique;gene expression;gene expression regulation;genetics;immunohistochemistry;liver;metabolism;mouse mutant;retina disease;Adipocytes;Animals;Biomarkers;Body Weights and Measures;Disease Models, Animal;Fatty Acid-Binding Proteins;Fluorescent Antibody Technique;Gene Expression;Gene Expression Regulation;Glucose Intolerance;Immunohistochemistry;Insulin;Kidney Diseases;Liver;Mice;Mice, Obese;Nitric Oxide Synthase Type II;Non-alcoholic Fatty Liver Disease;Proto-Oncogene Proteins c-akt;Reactive Oxygen Species;Retinal Diseases;Sterol Regulatory Element Binding Protein 1 | 公開日期: | 2021 | 卷: | 22 | 期: | 13 | 來源出版物: | International Journal of Molecular Sciences | 摘要: | Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozap-ine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine’s adverse metabolic effects—such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy—was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver dam-age, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food effi-ciency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin re-sistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 ex-pression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione pe-roxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention. ? 2021 by the author. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85108222939&doi=10.3390%2fijms22136680&partnerID=40&md5=ed6edfa1ace7b98355634d66ee3bc294 https://scholars.lib.ntu.edu.tw/handle/123456789/605990 |
ISSN: | 16616596 | DOI: | 10.3390/ijms22136680 |
顯示於: | 獸醫學系 |
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