title: Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system.
abstract: Sesamol, a nutritional component from sesame, possesses antioxidant, lipid lowering and antidepressant activities. Nonetheless, few studies report its effects on high-energy-dense diet-induced cognitive loss. The present research 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. 3 month-old 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. Morris water maze tests demonstrated that sesamol improved HFFD-elicited learning and memory loss. Sesamol was also found to attenuate neuron damage in HFFD-fed mice. Importantly, sesamol treatment up-regulated brain insulin signaling by stimulating IRS-1/AKT as well as ERK/CREB/BDNF pathways; meanwhile it down-regulated neuronal death signaling GSK3β and JNK. Moreover, sesamol also normalized mRNA expressions of neurotrophins including BDNF and NT-3, as well as expressions of mitochondrial metabolic and biogenesis related genes Sirt1 and PGC1α. Consistently, sesamol also reversed high-glucose-induced oxidized cellular status, mitochondrial membrane potential loss, insulin signaling inhibition and cell death in SH-SY5Y neuronal cells. Taken together, the current study proved that sesamol reduced western-diet-induced cognitive defects in a mouse model by inhibiting insulin resistance, normalizing mitochondrial function and cell redox status, and improving IRS/AKT cell surviving and energy metabolism regulating signaling. This compelling evidence indicated that sesamol is a potential nutritional supplement to prevent unhealthy-diet-induced learning and memory loss.
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Yali
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Qiao
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Wentong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Ren
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. xueboliu@aliyun.com.
authors.forename: Xuebo
authors.identifier: http://orcid.org/0000-0001-6370-2868
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements / Q000032:analysis; D005632:Fructose / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010636:Phenols / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D052117:Benzodioxoles; D007328:Insulin; D010636:Phenols; D005632:Fructose; C025583:sesamol; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1