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Background: Liraglutide, a GLP-1 receptor agonist, has recently been used to treat metabolic syndrome (MS) because of its anti-diabetic and anti-obesity effects. We have previously shown that Wistar Bonn Kobori diabetic and fatty (WBN/Kob-Leprfa, WBKDF) rats fed a high-fat diet (HFD) developed MS including marked obesity, hy-perglycemia, and dyslipidemia. To obtain further information on WBKDF-HFD rats as a severe MS model, we performed a pharmacological investigation into the anti-MS effects of liraglutide in this model.Methods: Seven-week-old male WBKDF-HFD rats were allocated to three groups (n = 8 in each group): a vehicle group, a low-dose liraglutide group, and a high-dose liraglutide group. They received subcutaneous injections of either saline or liraglutide at doses of 75 or 300 μg/kg body weight once daily for 4 weeks. Results: Results showed that liraglutide treatment reduced body weight gain and food intake in a dose-dependent manner. The marked hyperglycemia and the glucose tol-erance were also significantly ameliorated in the liraglutide-treated groups. Moreover, liraglutide also reduced the plasma triglyceride concentration and liver fat accumulation. Conclusions: The present study demonstrated that liraglutide could significantly al-leviate MS in WBKDF-HFD rats, and the reaction to liraglutide is similar to human patients with MS. WBKDF-HFD rats are therefore considered to be a useful model for research on severe human MS.