scholarly journals Risperidone Exacerbates Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Renal Impairment in Obese Mice

2021 ◽  
Vol 22 (1) ◽  
pp. 409
Author(s):  
Hsiao-Pei Tsai ◽  
Po-Hsun Hou ◽  
Frank-Chiahung Mao ◽  
Chia-Chia Chang ◽  
Wei-Cheng Yang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Renal Impairment ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Glucose Intolerance ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver

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.

scholarly journals Curcumin Improved Glucose Intolerance, Renal Injury, and Nonalcoholic Fatty Liver Disease and Decreased Chromium Loss through Urine in Obese Mice

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1132
Author(s):  
Geng-Ruei Chang ◽  
Wen-Tsong Hsieh ◽  
Lan-Szu Chou ◽  
Chen-Si Lin ◽  
Ching-Fen Wu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Glucose Intolerance ◽  
Renal Injury ◽  
Fatty Liver Disease ◽  
Renal Damage ◽  
Control Group ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver

Obesity-associated hyperglycemia underlies insulin resistance, glucose intolerance, and related metabolic disorders including type 2 diabetes, renal damage, and nonalcoholic fatty liver disease. Turmeric root is commonly used in Asia, and curcumin, one of its pharmacological components, can play a role in preventing and treating certain chronic physiological disorders. Accordingly, this study examined how high-fat diet (HFD)-induced hyperglycemia and hyperlipidemia are reduced by curcumin through changes in fatty liver scores, chromium distribution, and renal injury in mice. Relative to the control group, also fed an HFD, the curcumin group weighed less and had smaller adipocytes; it also had lower daily food efficiency, blood urea nitrogen and creatinine levels, serum alanine aminotransferase and aspartate aminotransferase levels, serum and hepatic triglyceride levels, and hepatic lipid regulation marker expression. The curcumin-treated obese group exhibited significantly lower fasting blood glucose, was less glucose intolerant, had higher Akt phosphorylation and glucose transporter 4 (GLUT4) expression, and had greater serum insulin levels. Moreover, the group showed renal damage with lower TNF-α expression along with more numerous renal antioxidative enzymes that included superoxide dismutase, glutathione peroxidase, and catalase. The liver histology of the curcumin-treated obese mice showed superior lipid infiltration and fewer FASN and PNPLA3 proteins in comparison with the control mice. Curcumin contributed to creating a positive chromium balance by decreasing the amount of chromium lost through urine, leading to the chromium mobilization needed to mitigate hyperglycemia. Thus, the results suggest that curcumin prevents HFD-induced glucose intolerance, kidney injury, and nonalcoholic fatty liver disease.

scholarly journals Imipramine Accelerates Nonalcoholic Fatty Liver Disease, Renal Impairment, Diabetic Retinopathy, Insulin Resistance, and Urinary Chromium Loss in Obese Mice

2021 ◽  
Vol 8 (9) ◽  
pp. 189
Author(s):  
Geng-Ruei Chang ◽  
Po-Hsun Hou ◽  
Chao-Min Wang ◽  
Jen-Wei Lin ◽  
Wei-Li Lin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Diabetic Retinopathy ◽  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Binding Protein ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver

Imipramine is a tricyclic antidepressant that has been approved for treating depression and anxiety in patients and animals and that has relatively mild side effects. However, the mechanisms of imipramine-associated disruption to metabolism and negative hepatic, renal, and retinal effects are not well defined. In this study, we evaluated C57BL6/J mice subjected to a high-fat diet (HFD) to study imipramine’s influences on obesity, fatty liver scores, glucose homeostasis, hepatic damage, distribution of chromium, and retinal/renal impairments. Obese mice receiving imipramine treatment had higher body, epididymal fat pad, and liver weights; higher serum triglyceride, aspartate and alanine aminotransferase, creatinine, blood urea nitrogen, renal antioxidant enzyme, and hepatic triglyceride levels; higher daily food efficiency; and higher expression levels of a marker of fatty acid regulation in the liver compared with the controls also fed an HFD. Furthermore, the obese mice that received imipramine treatment exhibited insulin resistance, worse glucose intolerance, decreased glucose transporter 4 expression and Akt phosphorylation levels, and increased chromium loss through urine. In addition, the treatment group exhibited considerably greater liver damage and higher fatty liver scores, paralleling the increases in patatin-like phospholipid domain containing protein 3 and the mRNA levels of sterol regulatory element-binding protein 1 and fatty acid-binding protein 4. Retinal injury worsened in imipramine-treated mice; decreases in retinal cell layer organization and retinal thickness and increases in nuclear factor κB and inducible nitric oxide synthase levels were observed. We conclude that administration of imipramine may result in the exacerbation of nonalcoholic fatty liver disease, diabetes, diabetic retinopathy, and kidney injury.

scholarly journals 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

2021 ◽  
Vol 22 (13) ◽  
pp. 6680
Author(s):  
Geng-Ruei Chang ◽  
Hsien-Yueh Liu ◽  
Wei-Cheng Yang ◽  
Chao-Min Wang ◽  
Ching-Fen Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Glucose Intolerance ◽  
Fatty Liver Disease ◽  
Oxygen Species ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver ◽  
Retinal Injury

Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine 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 damage, 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 efficiency; 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 resistance, 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 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, 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.

NR1H4 rs35724 G>C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Stefania Grimaudo ◽  
Paola Dongiovanni ◽  
Jussi Pihlajamäki ◽  
Mohammed Eslam ◽  
Hannele Yki-Järvinen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease and Urinary Chromium Loss in Obese Mice

2021 ◽  
Vol 14 (3) ◽  
pp. 267
Author(s):  
Geng-Ruei Chang ◽  
Po-Hsun Hou ◽  
Wei-Cheng Yang ◽  
Chao-Min Wang ◽  
Pei-Shan Fan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Glucose Intolerance ◽  
Fatty Liver Disease ◽  
Renal Damage ◽  
Liver Lipid ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver

Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, FABP4 mRNA, and SREBP1 mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

NR1H4 rs35724 G>C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

2021 ◽  
Author(s):  
Stefania Grimaudo ◽  
Paola Dongiovanni ◽  
Jussi Pihlajamäki ◽  
Mohammed Eslam ◽  
Hannele Yki‐Järvinen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

872 ADIPONECTIN IN NONALCOHOLIC FATTY LIVER DISEASE: CORRELATION WITH LIVER DAMAGE AND PNPLA3 GENOTYPE

2011 ◽  
Vol 54 ◽  
pp. S347-S348 ◽  
Author(s):  
L. Valenti ◽  
R. Rametta ◽  
E. Canavesi ◽  
M. Ruscica ◽  
A.L. Fracanzani ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Diospyros kaki and Citrus unshiu Mixture Improves Disorders of Lipid Metabolism in Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mi-Rae Shin ◽  
Sung Ho Shin ◽  
Seong-Soo Roh
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Diospyros Kaki ◽  
Citrus Unshiu ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) has been a major cause of a chronic liver disease over recent decades and increasing worldwide in parallel with the remarkable growth of obesity. In the present study, we investigate the ameliorative effects of PCM, a combination of Diospyros kaki fruit and Citrus unshiu peel mixture, on high-fat diet- (HFD-) induced NAFLD and clarify the potential mechanisms. PCM in HFD-fed mice was orally administered at a dose of 50 or 100 mg/kg subsequently for 2 months. Thereafter, lipid metabolism parameters and fat synthesis-related genes in the mouse liver were evaluated. Subsequently, body weight changes, liver weight, serum liver function and lipid profiles, and liver pathology were examined, and the relative levels of fatty acid synthesis and β-oxidation gene expression were evaluated by western blot. Serum AST, ALT, and TG levels in the HFD control mice were significantly higher than those of normal mice. Compared with HFD control mice, PCM supplementation increased phosphorylation of AMP-activated protein kinase (AMPK). Peroxisome proliferator-activated receptor (PPAR) α was significantly increased by PCM administration. Continuously, the activation of PPARα significantly elevated carnitine palmitoyltransferase 1 (CPT-1), a key enzyme in fatty acid β-oxidation, and mitochondrial uncoupling protein 2 (UCP-2), thermogenic regulatory genes, in PCM-treated mice compared with those of HFD control mice. Moreover, PCM inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 and its target genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Taken together, these effects were mediated through activation of AMPK. In the conclusion, PCM improved liver damage in HFD-fed mice and attenuated NAFLD by the activation of PPARα and the inhibition of SREBPs expression via AMPK-dependent pathways.

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