A Walnut Diet in Combination with Enriched Environment Improves Cognitive Function and Affects Lipid Metabolites in Brain and Liver of Aged NMRI Mice

Abstract

This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

Walnut Oligopeptide Delayed Improved Aging-Related Learning and Memory Impairment in SAMP8 Mice

“…Walnuts are nuts with a variety of health benefits that are consumed worldwide [ 25 , 26 , 27 , 28 ]. Among these, the nootropic effect of walnuts is widely recognized [ 29 , 30 , 31 ]. In the past, most studies attributed the benefits of walnuts to walnut oil, with little focus on WOPs.…”

Metabolomics Reveals Process of Allergic Rhinitis Patients with Single- and Double-Species Mite Subcutaneous Immunotherapy

“…Studies indicate that polyunsaturated fatty acids (PUFAs) and their metabolites can resolve inflammation, such as alpha-linolenic acid, linoleic acid and AA, but diet could affect the levels of these metabolites. Walnuts combined with physical activity reduced arachidonic acid-based oxylipin levels in the brain [50]. Supplementation with C. butyricum increased the concentrations of essential amino acids and flavor amino acids, as well as AA, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and total PUFAs in breast muscle [51].…”

Factors affecting variability in free oxylipins in mammalian tissues

“…This is in contrast to animal studies, likely due to the relatively much higher levels of PUFA enrichment that can be achieved in animal compared to human diets. LNA and ALA oxylipins can be substantially increased in mouse brain [42], rat muscle [19] and mouse adipose [20]. Interestingly, a higher LNA/ALA ratio (8:1 vs. 5:1) in vitro suppressed ALA oxylipins but did not affect LNA oxylipins in human T lymphocytes, indicating that the LNA and ALA oxylipins may be altered with large dietary differences in these essential fatty acids [43].…”