Characteristics of WBN/Kob diabetic fatty rats supplemented with a fructose-rich diet as a metabolic syndrome model: response to a GLP-1 receptor agonist

Junichi NAMEKAWA, Sayaka NEMOTO, Gaku SUNADA, Yuki TAKANASHI, Sakurako FUJIO, Mitsuyuki SHIRAI, ASAI Fumitoshi

The incidence of metabolic syndrome is rapidly increasing worldwide, and adequate animal models are crucial for studies on its pathogenesis and therapy. In the search of an adequate experimental model to simulate human metabolic syndrome, the present study was performed to examine the pharmacological response of WBN/Kob-Leprfa (WBKDF) rats supplemented with a fructose-rich diet (FRD) to liraglutide, a GLP-1 receptor agonist. Male WBKDF rats fed FRD at 7 weeks of age were divided into 3 groups, and administered liraglutide (75, 300 μg/kg subcutaneously) or saline (control group), once daily for 4 weeks. All rats in the control group became overweight, and developed hyperglycemia, hypertension and dyslipidemia as they aged. The rats given liraglutide exhibited a dose-dependent reduction in body weight, visceral fat content and food intake compared with control rats. In addition, liraglutide suppressed the development of hyperglycemia, hypertension and dyslipidemia. An intravenous glucose tolerance test revealed that liraglutide improved glucose tolerance, insulin secretion and insulin resistance. On histological examination, decreased hepatic fatty degeneration was observed in the liraglutide groups. The present study demonstrated that liraglutide protected against obesity, hyperglycemia, hypertension, dyslipidemia, and hepatic steatosis in WBKDF rats fed FRD, suggesting that WBKDF rats fed FRD may be a useful model to investigate the etiology of human metabolic syndrome.