Preventive Effects Of Sesamol On High Fat And High Fructose-induced Obesity And Insulin Resistance

With the development of society,residential dietary structure has altered,especially the increasing consumption of refined sugar and fat.Consequently,metabolic syndromes such as obesity,insulin resistence,and diabetes become global health risks.Sesamol,a liposoluble lignan extraction and prominent fragrance component in sesame oil,has been demonstrated to possess bioactivities such as antioxidant,anticancer and anti-inflammatory.Sesamol was also demonstrated to alleviate a high-fat diet induced hyperlipidemia and atherosclerosis.However,the underlying molecular mechanisms of sesamol attenuating high fat and high fructose diet feeding induced lipid metabolism disorder is still unclear.The aim of the current study was to investigate the effects of sesamol on obesity and obesity-related metabolic syndromes and the potential underlying mechanisms in mice fed with high fat and high fructose diet.The main investigations and results are as follows:(1)High fat and high fructose diet(HFFD)induced obese C57BL/6J mice were used to investigate the antiobesity effects of sesamol in vivo.Results showed that dietary supplementation of sesamol mitigated bodyweight gain but had no effects on energy intake,decreased the level of TG and TC,and decressed the insulin resistance through decreasing the level of fasting plasma glucose and fasting insulin.(2)In liver,sesamol decreased the liver weight and the level of TG and TC.The mRNA expressions of hepatic lipogenic including Pparg,Srebp1 c,Fasn,and Acaca were significantly decressed by sesamol supplementation.The mRNA expressions of genes mRNA that regulate lipolysis andmitochondria biogenesis including Ppara,Cpt1 a,Cpt2,Pgc1 a,Sirt1,COXII,and Tfam were incressed.Moreover,sesamol also attenuated cholesterol synthesis by downregulating cholesterol synthesis expressions of Hmgcr and Acat2.(3)In both eWAT and iWAT,sesamol also suppressed lipogenesis by decreasing expressions of Pparg,Srebp1 c,Fasn,and Acaca,and also elevating fat oxidation by increasing mitochondria lipid gene expressions of Ppara,Pgc1 a,Cpt1a,and Cpt2.Sesamol reduced “whitening” of BAT via decreasing lipid accumulation and improving mitochondria biogenesis and heat generating gene expressions,including Pgc1 a,Ucp1,Fgf21,COXII,and Tfam.(4)3T3-L1 preadipocytes were used to investigate the antiobesity effect of sesamol in vitro.Results showed that sesamol significantly suppressed MDI-induced 3T3-L1 preadipocytes differentiation and lipids accumulation.Moreover,in this study,two mitochondrial metabolic inhibitors antimycin A(complex III inhibitor)and oligomycin(ATP synthesis inhibitor)were employed to induce mitochondria impairments.JC-1 and DCF staining results indicated sesamol significantly prevented these two inhibitors induced MMP loss,balanced cellular redox status,and consequently suppressed adipogenesis in 3T3-L1 cells.