Topical Area: Dietary Bioactive Components
Objectives : Sesamol, an antioxidant lignan from sesame oil, possesses lipid lowering and neuroprotective bioactivities. Considering the distribution of sesamol in gut is much higher than brain after administration, the present work was aimed to elucidate the systemic protective effects of sesamol on dietary-induced cognitive deficits, and to determine the possible link between gut and brain.
Methods : Both wildtype and ApoE-/- mice were fed with high-fat diet (HFD) and treated with sesamol (0.05%, w/v) in drinking water for 10 weeks. The cognitive and anxiety behavioral assessment were evaluated by Morris-water maze, Y-maze, and elevated plus maze tests. The synapse ultrastructure was also detected by transmission electron microscope. Moreover, the alteration of gut microbiome and microbial metabolites short chain fatty acids (SCFAs) were also determined by 16S rDNA sequencing and GC, respectively.
Results : Sesamol prevented HFD-induced bodyweight gain, insulin resistance, and hyperlipidemia. However, the behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype but not ApoE deficient mice. Consistently, sesamol improved synapse ultrastructure and inhibited brain Aβ accumulation in brain in an ApoE-dependent manner. Moreover, sesamol prevented HFD-induced gut barrier damages and systemic inflammation. Sesamol also re-shaped gut microbiome and consequently improved the generation of microbial metabolites short chain fatty acids including acetate, propionate, and butyrate.
Conclusions : To summarized, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and the beneficial effects of sesamol on gut microbiota/metabolites could be translated into metabolic and neurodegenerative diseases treatment.
Funding Sources :