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Troglitazone prevents fatty changes of the liver in obese diabetic rats
1Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan.
Background And Aims:
Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats.
Methods:
A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age.
Results:
Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue.
Conclusion:
Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes.
Insights
Long-term troglitazone use in genetically obese diabetic rats improved metabolic derangements and prevented fatty liver disease. However, it did not impact colon tumorigenesis, suggesting a specific therapeutic window for this antidiabetic drug.
Area of Science:
- Pharmacology
- Hepatology
- Endocrinology
Background:
- Troglitazone, an antidiabetic drug, is associated with potential liver dysfunction.
- Concerns exist regarding troglitazone's activation of PPAR-gamma and its link to colon tumorigenesis.
Purpose of the Study:
- To investigate the long-term effects of troglitazone on liver and intestine health.
- To assess troglitazone's impact on metabolic parameters in genetically obese diabetic rats.
Main Methods:
- Genetically obese diabetic (OLETF) and control (LETO) rats were fed a troglitazone-rich diet or standard chow.
- Serum glucose, insulin, AST, ALT, cholesterol, and triglycerides were measured.
- Liver and intestine histology was examined at 72 weeks of age.
Main Results:
- Troglitazone normalized glucose and insulin levels in OLETF rats and reduced liver weight, cholesterol, and triglycerides.
- No significant changes in AST or ALT levels were observed.
- Troglitazone prevented fatty liver changes in OLETF rats but did not affect colon polyp formation.
Conclusions:
- Long-term troglitazone administration ameliorates metabolic abnormalities and hepatic steatosis in genetically obese diabetic models.
- The drug's effects on the colon were not significant, warranting further investigation into its specific mechanisms and safety profile.