摘要:Background: Flavonoids are multi-functional bioactive compounds that have been used as natural compounds against various diseases. Citrus fruit is an important source for bioactive flavonoids with potential anti-obesity benefits. Methods: To determine the anti-obese effects of citrus peel, a 45% high fat diet-induced obesity (DIO) model using C57BL/6 mice was prepared for 10 weeks and then treated orally for 12 weeks with ethanol extracts of citrus peel (300 mg/kg, CP). CP was compared with normal chow diet (C), high fat diet (HF), and the anti-obesity drug orlistat (30 mg/kg, O) as a positive control. HF caused increases in lipid accumulation, body weight gain, and hepatic toxicity compared with the C group. Results: CP treatment reduced body weight gain and decreased epididymal fat, mesenteric fat, and plasma and hepatic TG levels in a similar manner as O treatment. Besides, CP was comparatively more effective than O at increasing high density lipoprotein cholesterol (HDL-c) while reducing hepatic toxicity, which is caused by HF. Fat accumulation in adipose tissue was decreased by CP treatment because of up-regulation of specific lipolysis enzymes such as HSL and AMPK and down-regulation of adipogenesis related genes such as C/EBPα and ACC. The proinflammatory cytokines, TNF-α and IL-6, which are the key factors for regulation of inflammation, were significantly decreased by CP. Conclusion: CP may be a potential natural source for new anti-obesity candidate because of its inhibitory effect on fat synthesis-related inflammation and its positive effect on lipolysis activation.