Kivonat:
BACKGROUND AND PURPOSE: Incidence and severity of obesity is increasing worldwide. To date, efficient and safe pharmacological tools to treat or prevent obesity have not been developed. Certain monoamine-oxidase (MAO) inhibitors have been shown to reduce body weight, although their effect on metabolic parameters have not been investigated. Here we assessed the effect of a widely used, selective MAO-B inhibitor, selegiline, on metabolic parameters in high-fat, high-sucrose diet-induced rat model of obesity. EXPERIMENTAL APPROACH: Male Long-Evans rats were fed with control (CON) or high-fat (20%), high-sucrose (15%) diet (HFS) for 25 weeks. From week 16 groups of animals received subcutaneous injections of 0.25 mg kg(-1) selegiline (CON+S and HFS+S) or vehicle (CON, HFS) once daily. KEY RESULTS: Selegiline decreased whole body fat, subcutaneous and visceral adiposity as measured by computer tomography and epididymal fat weight in the HFS group as compared to HFS placebo animals without influencing body weight. Oral glucose tolerance test and insulin tolerance test results showed impaired glucose homeostasis in HFS and HFS+S groups despite unchanged insulin levels in the blood plasma and pancreas. HFS induced expression of Srebp-1c, Glut1, and Mip1alpha in adipose tissue, which was alleviated by selegiline treatment. CONCLUSION AND IMPLICATIONS: This is the first demonstration that selegiline reduces adiposity, alteration in adipose tissue energy metabolism and adipose inflammation induced by HFS diet without affecting the increase in body weight, impairment of glucose homeostasis, or behaviour. These results suggest the potential benefit of selegiline to mitigate harmful effects of visceral adiposity.
