Prevention of Diabetes by Fenofibrate in OLETF Rats: Hepatic Mechanism for Reducing Visceral Adiposity

2 , Mi-Kyoung Park , Mi-Kyoung Park , Mi-Kyoung Park , Mi-Kyoung Park - Abstract - - Abstract - - Abstract - - Abstract - Background: The aim of this study is to evaluate the hepatic mechanism of fenofibrate that has the diabetes protective action in rats. Methods: We chose OLETF rats and divided them into three groups. Fenofibrate (DF) group was fed with diet and fenofibrate (300 mg/kg/day). Paired feeding (Dd) group and free diet (DD) group were fed with diet. After 36 weeks of treatment, all the rats were sacrificed. Results: The fasting blood glucose level of DF group (8.5 ± 0.9 mmol/L) showed normal. The fasting blood glucose level of Dd group (22.4 ± 3.0 mmol/L) and DD group (16.9 ± 3.7 mmol/L) showed significantly increased than that of DF group ( P < 0.01, respectively). The body weight, visceral adipose tissue and subcutaneous adipose tissue of DF group were significantly decreased compared to those of Dd and DD groups ( P < 0.01, P < 0.05, P < 0.05). DF group showed significantly increased state-3 respiration rate, ATP synthetic activity, state-4 respiration rate and their blood β-keton body levels than those of control groups ( P < 0.01, respectively). DF group showed normal morphology of hepatocytes but DD and Dd groups showed hepatic steatosis with mitochondrial swellings. Conclusion: Chronic fenofibrate treatment prevents the development of diabetes in OLETF rats with inhibiting gain of body weight and abdominal adiposity. The hepatic mechanism for reducing visceral adiposity is that fenofibrate leads to increasing oxidative phosphorylation, uncoupling and ketogenesis as well as increasing beta-oxidation of fatty acids. Moreover, fenofibrate treatment prevents the development of hepatic steatosis. (J Kor Diabetes