Thinned young apple powder prevents obesity-induced neuronal apoptosis via improving mitochondrial function of cerebral cortex in mice.

Mitochondrial dysfunction is one of the triggers for obesity-induced neuron apoptosis. Thinned young apple is getting more attention on account of the extensive biological activities because of rich polyphenols and polysaccharides. However, the neuroprotective effect of thinned young apple powder (YAP) is still unclear. The aim of the present study was to investigate the preventive effect of YAP on obesity-induced neuronal apoptosis. C57BL/6J male mice were divided into 5 groups, control (CON), high fat diet (HFD), HFD + orlistat (ORL), HFD + low-dose young apple powder (LYAP) and HFD + high-dose young apple powder (HYAP) groups and intervened for 12 weeks. It was found that the YAP effectively reduced body weight gain. Importantly, the levels of pro-apoptosis protein were lower in LYAP and HYAP groups than the HFD group, such as Bak/Bcl2 and cleaved caspase3/caspase3. Pathway analysis based on untargeted metabolomics suggested that YAP alleviated obesity-induced neuronal apoptosis by three main metabolic pathway including arginine metabolism, citrate cycle (TCA cycle) and glutathione metabolism. Meanwhile, YAP improved the protein expression of mitochondrial respiratory chain complex, maintained the homeostasis of TCA cycle intermediates, protected the balance of mitochondrial dynamics and alleviated lipid accumulation. In addition, the levels of several antioxidants in cerebral cortex were higher in HYAP group than the HFD group like superoxide dismutase (SOD) and catalase (CAT). In summary, YAP supplementation suppressed neuronal apoptosis in the cerebral cortex of HFD-induced obesity mice by improving mitochondrial function and inhibiting oxidative stress.

The effect of n-3 polyunsaturated fatty acid supplementation on cognitive function outcomes in the elderly depends on the baseline omega-3 index.

Both epidemiological and preclinical studies have shown the benefits of n-3 polyunsaturated fatty acid (n-3 PUFA) on dementia and cognitive impairment, yet the results of clinical randomized controlled trials (RCTs) performed to date are conflicting. The difference in the baseline omega-3 index (O3i) of subjects is a potential cause for this disparity, yet this is usually ignored. The present meta-analysis aimed to evaluate the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on cognitive function in the elderly and the role of baseline O3i. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to June 27th, 2023. The mean changes in the mini-mental state examination (MMSE) score were calculated as weighted mean differences by using a fixed-effects model. Fifteen random controlled trials were included in the meta-analysis. Pooled analysis showed that n-3 PUFA supplementation did not significantly improve the MMSE score (WMD = 0.04, [-0.08, 0.16]; Z = 0.62, P = 0.53; I2 = 0.00%, P(I2) = 0.49). Out of the 15 studies included in the meta-analysis, only 7 reported O3i at baseline and outcome, so only these 7 articles were used for subgroup analysis. Subgroup analysis showed that the MMSE score was significantly improved in the higher baseline O3i subgroup (WMD = 0.553, [0.01, 1.095]; I2 = 0.00%, P(I2) = 0.556) and higher O3i increment subgroup (WMD = 0.525, [0.023, 1.026]; I2 = 0.00%, P(I2) = 0.545). The overall effect demonstrated that n-3 PUFA supplementation exerted no improvement on global cognitive function. However, a higher baseline O3i and higher O3i increment were associated with an improvement in cognitive function in the elderly.

Dendrobium officinale polysaccharide prevents neuronal apoptosis via TET2-dependent DNA demethylation in high-fat diet-induced diabetic mice.

Dendrobium officinale polysaccharide (DP) has the potential function to prevent diabetes-induced neuronal apoptosis, whereas the mechanism is not completely clear. Ten eleven translocation dioxygenase 2 (TET2) is one of the most important therapeutic target for repairing neuronal damage in diabetic mice. The aim of the present study was to investigate whether DP could prevent neuronal apoptosis by regulating TET2 in the brain of HFD-induced diabetic mice. C57BL/6J mice were randomly divided into four groups (n = 12), control group (CON), high-fat diet group (HFD, negative control), metformin group (MET, positive control), and DP group (DP). Compared with HFD group, the neuronal apoptosis of brain was significantly lower in the DP group. The levels of TET2 protein, 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were significantly lower in the HFD group than in both the DP and CON groups in the cerebral cortex of mice. The ratio of p-AMPK/AMPK and α-KG/(fumaric acid + succinic acid) were significantly lower in the HFD group than in the other groups. The present study suggests that DP has a preventive effect on diabetes-induced neuronal apoptosis by regulating TET2 function through improving phosphorylate AMPK and mitochondrial function, thus remodeling DNA epigenetics profile of mice brain.