Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.

The rates of obesity and obesity-related diseases continue to increase worldwide, classifying obesity as a global epidemic. Endogenous opioids have been implicated in influencing feeding behavior; however, the role of each opioid peptide is still only partially characterized. Therefore, we assessed the role of the proopiomelanocortin (POMC)-derived peptide beta-endorphin (β-END) in long-term high-fat diet (HFD) feeding and glucose homeostasis and assessed if sex-related differences exist in these processes. Male and female mice lacking the ability to produce β-END and their respective controls were subjected to a 12-week HFD consumption to determine the role of the opioid peptide in food intake and glucose homeostasis. Body weight and food intake were measured weekly for twelve weeks. At weeks 6 and 12, plasma glucose levels were measured using an oral glucose tolerance test. Here, we report that male β-END deficient mice gained more weight and consumed more calories than their wildtype controls; however, this difference was not observed in the female mice. Regardless of genotype, female mice consumed more calories per body weight when compared to male mice despite their smaller body weights. Moreover, our findings suggest differences in glucose homeostasis between the wildtype and knockout mice and that these were only observed at week six but not at week 12. Overall, our study suggests that endogenous β-END may play a role in controlling body weight, feeding behavior, and glucose homeostasis and that sex-related differences may exist in this regard.

Administration of crude polysaccharides extract from natural product is a promising gut microbiota-targeted approach to preventing obesity and associated metabolic disorders. Dietary restrictions can change the type and number of gut bacteria, which is an important factor in delaying the onset and burden of diseases. This study aimed to investigate the effects of high-yield crude polysaccharides from Cordyceps militaris (CMP) on high-fat diet (HFD) mice model and the gut microbiota community assembly, and to identify whether selenium (Se) addition would improve CMP action mode during cultivation. We found that the CMP treatment ameliorated adipose and liver pathologic morphology and fat accumulation in obese mice, while, SeCMP intervention was not superior than CMP in body mass gain, but notably decreasing serum triglyceride level increased by HFD. The upregulated expression of gene Cyp7a1 in liver and protein UCP1 in brown adipose tissue (BAT) preliminary indicated that the effect might relate to bile acids (BAs) metabolism pathway and thermogenesis. In addition, CMP showed a drastic decrease in the gut microbes which positively correlated with dyslipidemia parameters. Our result reveals the potential of CMP to be used as functional food in the prevention of diet-induced adipose and liver steatosis, so does SeCMP has outstanding capacity of improving dyslipidemia.