The Effect Of Active Ingredients Of Nobiletin And Hesperidin On Fat Accumulation

Obesity is a major health issue in developed countries,and recent years it became a worldwide health problem including developing and undeveloped countries.Because obesity can lead to the obesity-related diseases such as type-2 diabetes,cardiovascular disorders and certain cancers.Nobiletin and hesperidin as two constituents in orange peels,are often used in the reseach of anti-tumor,anti-inflammation and anti-hypertension.Recently,they have also been employed to study lipid metabolic disorders such as type 2 diabetes and atherosclerosis.Therefore,the effects of nobiletin and hesperidin on the weight loss are interesting.In order to detect whether they posses the potential ability of the anti-obesity,the 3T3-L1 cells and Caenorhabditis elegans(C.elegans)were used to investigate the effects of nobiletin and hespeidin on inhibiting adipogenesis.The results are as follows:1.As shown in the Oil-Red O staining and the adipogenesis assay,nobiletin per se promotes the fatty accumulation in the 3T3-L1 cells.Furthermore,real time PCR assay shows that nobiletin enhance the triglyceride accumulation of the 3T3-L1 cells by upregulateing the expression of the adipogenic genes.2.By applying LY294002,a selective inhibitor of Akt/PKB,to inhibit PI3K,the Oil-Red O staining and the adipogenesis assay show the ability that nobiletin increase the adipogenesis in the 3T3-L1 cells was blocked.Furthermore,real time PCR and western Immunoblotting assay show nobiletin promotes the adipogenesis by PI3K/Akt pathway.3.In cocktail induction media,the ability that nobiletin can inhibit the fatty accumulation in the 3T3-L1 cells was determined by the adipogenesis and real time PCR assays.What's more,by the various inducer combinations,nobiletin decreases the adipogenesis of the 3T3-L1 cells only by IBMX and DEX or insulin mixture induction.However,by blocking the cAMP pathways,nobiletin can not alter the fatty accumulation in the 3T3-L1 cells,suggesting that nobiletin suppresses adipogenesis of 3T3-L1 cells not by IBMX and DEX or insulin Mixture induction.4.The adipogenesis and real time PCR assays show that nobiletin restores the adipogenesis of the 3T3-L1 cells by utilizing the Compound C,the results indicate that nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase(AMPK),furthermore,the western blot assay shows that nobiletin might inhibit adipogenesis of 3T3-L1 cells via the suppression of PI3K/Akt regulated by AMPK.5.It was firstly found that hesperidin can regulate the adipogenesis of C.elegans by regulating the expression of FAT-6 and FAT-7 gene in C.elegans,indicating that FAT-6 and FAT-7 gene are important to the adipogenesis of the C.elegans.According to the above results,firstly,the model that nobiletin regulates the fatty accumulation in the 3T3-L1 cells by PI3K/Akt pathway is proposed,which maybe advance the understanding about the regulation of the fatty accumulation of nobiletin in the 3T3-L1 cells and provide a deep insight in the area.Secondly,hesperidin can inhibit the adipogenesis of the C.elegans,suggesting that FAT-6 and FAT-7 gene are important to the adipogenesis of the C.elegans.