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Issue 2, 2017
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Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system

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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.

Graphical abstract: Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system

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Publication details

The article was received on 24 Oct 2016, accepted on 03 Jan 2017 and first published on 05 Jan 2017


Article type: Paper
DOI: 10.1039/C6FO01562J
Food Funct., 2017,8, 710-719

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    Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system

    Z. Liu, Y. Sun, Q. Qiao, T. Zhao, W. Zhang, B. Ren, Q. Liu and X. Liu, Food Funct., 2017, 8, 710
    DOI: 10.1039/C6FO01562J

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