Risperidone exacerbates glucose intolerance, nonalcoholic fatty liver disease, and renal impairment in obese mice
Journal
International Journal of Molecular Sciences
Journal Volume
22
Journal Issue
1
Pages
1-21
Date Issued
2021
Author(s)
Tsai H.-P
Abstract
Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
adiponectin; alanine aminotransferase; aspartate aminotransferase; catalase; creatinine; fatty acid; fatty acid binding protein 4; fatty acid synthase; glucose transporter 4; glutathione peroxidase; hydroxymethylglutaryl coenzyme A reductase kinase; insulin; leptin; messenger RNA; nitrogen; patatin like phospholipid domain containing protein 3; phospholipid; protein kinase B; risperidone; sterol regulatory element binding protein 1; superoxide dismutase; triacylglycerol; unclassified drug; urea; adiponectin; alanine aminotransferase; aspartate aminotransferase; calcium independent phospholipase A2; catalase; copper zinc superoxide dismutase; DNA binding protein; fatty acid binding protein; fatty acid synthase; GLUT4 enhancer factor, mouse; glutathione peroxidase; insulin; PNPLA3 protein, mouse; protein kinase B; risperidone; Sod1 protein, mouse; sterol regulatory element binding protein 1; transcription factor; triacylglycerol; alanine aminotransferase level; animal cell; animal experiment; animal model; animal tissue; Article; body composition; comparative study; controlled study; disease exacerbation; drug effect; enzyme activity; epididymis fat; fat pad; food intake; glucose homeostasis; glucose intolerance; glucose tolerance; insulin blood level; insulin resistance; kidney dysfunction; kidney function; kidney injury; kidney tissue; lipid diet; liver function; liver injury; liver tissue; male; mouse; nonalcoholic fatty liver; nonhuman; obesity; protein expression; protein phosphorylation; regulatory mechanism; retroperitoneal fat; triacylglycerol blood level; urea nitrogen blood level; adipocyte; animal; blood; body weight; C57BL mouse; cytology; enzymology; genetics; glucose intolerance; metabolism; mouse mutant; nonalcoholic fatty liver; phosphorylation; Adipocytes; Adiponectin; Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Catalase; DNA-Binding Proteins; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Glucose Intolerance; Glutathione Peroxidase; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Phospholipases A2, Calcium-Independent; Phosphorylation; Proto-Oncogene Proteins c-akt; Risperidone; Sterol Regulatory Element Binding Protein 1; Superoxide Dismutase-1; Transcription Factors; Triglycerides
SDGs
Other Subjects
adiponectin; alanine aminotransferase; aspartate aminotransferase; catalase; creatinine; fatty acid; fatty acid binding protein 4; fatty acid synthase; glucose transporter 4; glutathione peroxidase; hydroxymethylglutaryl coenzyme A reductase kinase; insulin; leptin; messenger RNA; nitrogen; patatin like phospholipid domain containing protein 3; phospholipid; protein kinase B; risperidone; sterol regulatory element binding protein 1; superoxide dismutase; triacylglycerol; unclassified drug; urea; adiponectin; alanine aminotransferase; aspartate aminotransferase; calcium independent phospholipase A2; catalase; copper zinc superoxide dismutase; DNA binding protein; fatty acid binding protein; fatty acid synthase; GLUT4 enhancer factor, mouse; glutathione peroxidase; insulin; PNPLA3 protein, mouse; protein kinase B; risperidone; Sod1 protein, mouse; sterol regulatory element binding protein 1; transcription factor; triacylglycerol; alanine aminotransferase level; animal cell; animal experiment; animal model; animal tissue; Article; body composition; comparative study; controlled study; disease exacerbation; drug effect; enzyme activity; epididymis fat; fat pad; food intake; glucose homeostasis; glucose intolerance; glucose tolerance; insulin blood level; insulin resistance; kidney dysfunction; kidney function; kidney injury; kidney tissue; lipid diet; liver function; liver injury; liver tissue; male; mouse; nonalcoholic fatty liver; nonhuman; obesity; protein expression; protein phosphorylation; regulatory mechanism; retroperitoneal fat; triacylglycerol blood level; urea nitrogen blood level; adipocyte; animal; blood; body weight; C57BL mouse; cytology; enzymology; genetics; glucose intolerance; metabolism; mouse mutant; nonalcoholic fatty liver; phosphorylation; Adipocytes; Adiponectin; Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Catalase; DNA-Binding Proteins; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Glucose Intolerance; Glutathione Peroxidase; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Phospholipases A2, Calcium-Independent; Phosphorylation; Proto-Oncogene Proteins c-akt; Risperidone; Sterol Regulatory Element Binding Protein 1; Superoxide Dismutase-1; Transcription Factors; Triglycerides
Type
journal article