Abstract
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.
Highlights
Obesity is observed to be in a close relationship with low-grade systemic inflammation, which is considered to have a tendency towards the progression of insulin resistance, hyperglycemia, and related metabolic disorders [1] [2]
A comparison of the high fat diet (HF) and Citrus Peel (CP) groups shows a dramatic decrease in mesenteric and epididymal fat weights with CP treatment, but there were no significant difference in subcutaneous fat weight between the CP and HF groups
Our results show that the CP treatment is comparable with that of orlistat treatment, is not as good as orlistat’s effects on the reduction of fat accumulation, and provide sufficient credibility that CP is a natural source for new anti-obesity candidate
Summary
Obesity is observed to be in a close relationship with low-grade systemic inflammation, which is considered to have a tendency towards the progression of insulin resistance, hyperglycemia, and related metabolic disorders [1] [2]. Elevated levels of pro-inflammatory adipokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are mainly associated with increasing adiposity and malfunctioning of adipocytes in obesity [5]. In the TNF-alpha signaling pathway, AMPK is an important target and TNF-α has a suppressive effect on the AMPK signaling pathway, which regulates lipolysis and fat oxidation in adipocytes [6]. HF caused increases in lipid accumulation, body weight gain, and hepatic toxicity compared with the C group. CP was comparatively more effective than O at increasing high density lipoprotein cholesterol (HDL-c) while reducing hepatic toxicity, which is caused by HF. Conclusion: CP may be a potential natural source for new anti-obesity candidate because of its inhibitory effect on fat synthesisrelated inflammation and its positive effect on lipolysis activation
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