Exercise has profound benefits for brain function in animals and humans. In rodents, voluntary wheel running increases the production of new neurons and upregulates neurotrophin levels in the hippocampus, as well as improving synaptic plasticity, memory function and mood. The underlying cellular mechanisms, however, remain unresolved. Recent research indicates that peripheral organs such as skeletal muscle, liver and adipose tissue secrete factors during physical activity that may influence neuronal function. Here we used an in vitro cell assay and proteomic analysis to investigate the effects of proteins secreted from skeletal muscle cells on adult hippocampal neural progenitor cell (aNPC) differentiation. We also sought to identify the relevant molecules driving these effects. Specifically, we treated rat L6 skeletal muscle cells with the AMP-kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) or vehicle (distilled water). We then collected the conditioned media (CM) and fractionated it using high-performance liquid chromatography (HPLC). Treatment of aNPCs with a specific fraction of the AICAR-CM upregulated expression of doublecortin (DCX) and Tuj1, markers of immature neurons. Proteomic analysis of this fraction identified proteins known to be involved in energy metabolism, cell migration, adhesion and neurogenesis. Culturing differentiating aNPCs in the presence of one of the factors, glycolytic enzyme glucose-6-phosphate isomerase (GPI), or AICAR-CM, increased the proportion of neuronal (Tuj1+) and astrocytic, glial fibrillary acidic protein (GFAP+) cells. Our study provides further evidence that proteins secreted from skeletal muscle cells may serve as a critical communication link to the brain through factors that enhance neural differentiation.
Although several evidence has suggested the impact of exercise on the prevention of aging phenotypes, few studies have been conducted on the mechanism by which exercise alters the immune-cell profile, thereby improving metabolism in senile obesity. In this study, we confirmed that 4-week treadmill exercise sufficiently improved metabolic function, including increased lean mass and decreased fat mass, in 88-week-old mice. The expression level of the senescence marker p16 in the white adipose tissue (WAT) was decreased after 4-weeks of exercise. Exercise induced changes in the profiles of immune-cell subsets, including natural killer (NK) cells, central memory CD8
+
T cells, eosinophils, and neutrophils, in the stromal vascular fraction of WAT. In addition, it has been shown through transcriptome analysis of WAT that exercise can activate pathways involved in the interaction between WAT and immune cells, in particular NK cells, in aged mice. These results suggest that exercise has a profound effect on changes in immune-cell distribution and senescent-cell scavenging in WAT of aged mice, eventually affecting overall energy metabolism toward a more youthful state.
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