Obesity-related type 2 diabetes has reached epidemic level globally. Aged citrus peel (chenpi) has long been used as a food ingredient and herbal medication against obesity and inflammation with unidentified active constituents. Compared to fresh citrus peel, chenpi is uniquely enriched with 5-demethylated polymethoxyflavones (5-OH PMFs). In this study, chenpi extract was prepared by a continuous phase transition extraction method with n-butane as the solvent. Oral administration of 0.25 and 0.5% chenpi extract in food over 15 weeks prevented high-fat diet-induced body weight gain, hepatic steatosis, and diabetic symptoms in mice. Such beneficial effects were not caused by reduction in food intake or nutrient absorption. Moreover, supplementation of chenpi extract significantly increased AMP-activated protein kinase (AMPK) activity in adipose tissue, which correlates with the smaller adipocyte size and lower adipose mass in mice. Further study showed that in 3T3-L1 cell model system, chenpi extract significantly reduced intracellular lipid accumulation in differentiating mouse adipocytes without significantly affecting cell viability and proliferation. The reduction in lipid accumulation in adipocytes correlated with down-regulation of adipogenic transcription factors and AMPK activation, suggesting that chenpi extract may directly affect lipogenesis in adipose tissue. Intriguingly, two types of chenpi extract samples varying in 5-OH PMF content exhibited differential effects on lipid accumulation in differentiating adipocytes, suggesting the content of 5-OH PMFs could affect the anti-lipogenic activity of chenpi extract. Overall, this study demonstrated that 5-OH PMFs-enriched chenpi can effectively promote lipid metabolism in adipose tissue and liver, which in turn favorably improved insulin sensitivity, glycemic control and plasma lipid profile. Reducing ectopic lipid accumulation is believed to be one of the best approaches for treating type 2 diabetes by targeting an underlying cause of insulin resistance. The present study provides strong evidence that chenpi extract, as a safe food processing by-product, could be a novel nutraceutical for the prevention of obesity and diabetic symptoms.

Prevention of obesity and type 2 diabetes with aged citrus peel (chenpi) extract

253rd National Meeting (2017)

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