Effects Of Sesamol On High Fat And Fructose Diet-induced Brain Insulin Resistance And Cognitive Disorders

With the development of society economic as well as the people’s life quality,the high caloric diet,such as high fat and high fructose diet,has become the international popular dietary patterns.These unhealthy diet patterns lead to many health problems such as obesity,diabetes and cognitive dysfunction,which is gaining increasing attention day by day.It has become a hot research topic in food nutrition research field that discovering functional food components from fruits,vegetables,and food oil to intervene chronic metabolic diseases such as obesity.Sesamol,a nutritional lignans component from sesame which is one of the Chinese traditional oil,possesses antioxidant,lipid lowering,anti-inflammatory and neuroprotection biological activities.Nonetheless,the underlying molecular mechanism of its effects on high-energy-dense diet-induced cognitive loss is not clear.Therefore,the present research was aimed to elucidate the action of sesamol on high-fat and high-fructose(HFFD)“western”-diet-induced central nervous system insulin resistance and learning and memory impairment,and further determined the possible underlying mechanism.The main results are as follows:(1)The C57BL/6J mice were divided into 3 groups with/without sesamol in the drinking water(0.05%,w/v)and standard diet,HFFD,and HFFD with sesamol supplementation.It was found that sesamol suppressed HFFD-induced increasing of body weight as well as liver tissue.Besides,sesamol supplementation revered the fast blood glucose,fast insulin and HOMA-IR values.Morris water maze tests demonstrated that sesamol improved HFFD-elicited learning and memory loss.In addition,sesamol was also found to attenuate neuron damage and promote neurogenesis in hippocampus in HFFD-fed mice which performed by immunohistochemistry and immunofluorescence.Importantly,sesamol supplementation up-regulated ERK/CREB/BDNF pathways in the brain of mice,as well as improved the mRNA and protein expressions of neurotrophins.(2)The underlying molecular mechanism of prevention effects of sesamol on HFFD-induced insulin resistance and cognitive disorders was explored.The study demonstrated that sesamol treatment up-regulated brain insulin signaling by stimulating IRS-1/AKT pathways,increasing the protein and mRNA expressions of GLUT4 as well as the mRNA expressions of mitochondrial metabolic and biogenesis related genes Sirt1 and PGC-1α,and improving the energy metabolism in the brain.Meanwhile,sesamol down-regulated GSK-3β and JNK related to neuronal death signaling.Moreover,sesamol also reduced inflammation factor mRNA expressions including TNF-α and IL-1β in the brain of mice.(4)Sesamol improved 100 mmol glucose-induced in SH-SY5 Y neuronal cells.It was found that sesamol up-regulated insulin signaling through the IRS/AKT pathway.Besides,sesamol treatment can reduced oxidized cellular status and H2O2,improving the reduction of the mitochondrial membrane potential which caused by high glucose-induced damage of the insulin signaling in SH-SY5 Y neuronal cells.This experiment reveals that sesamol alleviated western dietary pattern induced IR signal pathways defects,learning and memory function loss of the brain,and the neurotrophic factors suppression in brain,which provides the basic theory for development and application of the functional food of sesamol.