Modulation Effects Of Ilex Latifolia Thunb On High-fat Diet-induced Obesity And Metabolic Syndrome

Obesity has become one of the most important health problems worldwide,and has also become an important factor in harmful to public health and people’s lives in China.Meanwhile,obesity is the physiological basis of many chronic metabolic diseases,including type 2 diabetes and cardiovascular disease.Therefore,the prevention and treatment of obesity are particularly important.Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects.Therefore,searching naturally-occurring,high effect healthy food and safe medicine for adiposity has been the roject that global science and technology field and product field care mostly.Green tea and kuding tea are two of the most popular beverages in China.Green tea has been well studied for its health benefits in previous reports,but there is few data on the biological functions of kuding tea.Kuding tea has been widely used in Chinese medicine for more than 2,000 years as a beverage to quench thirst,remove phlegm,refresh the mind and improve eyesight.Ilex latifolia Thunb is one of the main breed varieties of kuding tea.Our study systematically investigated the effects of Ilex latifolia Thunb on high-fat diet-induced obesity and chronic inflammation by vitro and vivo experiments.The anti-obesity effect of aqueous extract of Ilex latifolia Thunb(KD)was tested using OP9 cells initially.Its inhibitory ability towards lipid droplet accumulation was evaluated through oil red O stain,and quantitative real-time PCR was used to detect the lipogenesis-related genes.In vivo experiment,mice were randomly divided into normal diet group,high-fat diet(HFD)group and HFD administered with KD group.Throughout the feeding course,body weight was monitored weekly and at the end of feeding course,we performed glucose tolerance test,insulin tolerance test and metabolic chamber experiment.After sacrificing the mice,we collected the blood,liver,epididymal and brown adipose tissues to determine the insulin resistance-related and adipose inflammation-related indicators.The main conclusions of the study are as follows:(1)Ilex latifolia Thunb inhibits adipocyte differentiationOil red O stain results showed that the aqueous extract of Ilex latifolia Thunb significantly inhibited the lipid droplet accumulation and cell differentiation.qPCR results showed that the aqueous extract of Ilex latifolia Thunb significantly decreased the transcription level of lipogenesis-related genes PPARgamma and FAS.(2)Ilex latifolia Thunb alleviates HFD-induced obesityMice body weight and indices of epididymal fat pad versus body weight results showed that Ilex latifolia Thunb significantly reduced the body weight gain induced by HFD and indices of epididymal fat pad versus body weight.Hematoxylin and eosin(H&E)staining of adipose tissues showed that Ilex latifolia Thunb could reduce adipocyte size.(3)Ilex latifolia Thunb enhances energy expenditureMetabolic chamber showed that Ilex latifolia Thunb enhanced O2 consumption,CO2 release,spontaneous locomotor activity and heat production.These data suggest that Ilex latifolia Thunb attenuated HFD-induced obesity due to enhanced energy expenditure.(4)Ilex latifolia Thunb protects against hepatic steatosisMice liver weight,TG level and sections results showed that Ilex latifolia Thunb could reduce liver lipid accumulation.Ilex latifolia Thunb could significantly decrease serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-c)and low-density lipoprotein cholesterol(LDL-c)levels.(5)Ilex latifolia Thunb improves insulin sensitivity and glucose homeostasisIlex latifolia Thunb could significantly reduce the fasting glucose and serum insulin levels of mice fed HFD and increase adiponectin expression levels in adipose tissue and serum.GTT and ITT results also showed that Ilex latifolia Thunb could improve the obesity-related insulin resistance and glucose intolerance.(6)Ilex latifolia Thunb decreases the expression of lipogenic genesBoth qPCR and western blot results showed that Ilex latifolia Thunb inhibited lipogenic signaling as evidenced by lower expression of PPARgamma and SREBP-1c in liver and adipose tissue.Moreover,Ilex latifolia Thunb increased AMPK phosphorylation supporting enhanced energy expenditure.(7)Ilex latifolia Thunb decreases inflammationLuminex results showed that Ilex latifolia Thunb reduced pro-inflammatory factors(IL-6,IFN-γ,IL-1β,IL-2 and IL-17)and increased anti-inflammatory factors(IL-4 and IL-10)levels.HFD increased phosphorylated p38 and p65 levels in adipose tissue and Ilex latifolia Thunb could decrease inflammation-related p38 and p65 signaling.Moreover,Ilex latifolia Thunb reversed the high levels of leptin and PAI-1 adipokines.In conclusion,our study proved that Ilex latifolia Thunb played protective roles in obesity by inhibiting adipogenesis and increasing energy expenditure.Additionally,Ilex latifolia Thunb could restore the chronic inflammation and obesity-related insulin resistance.These results provided a foundation for the beneficial effect of Ilex latifolia Thunb on obesity and related metabolic syndrome.