Multi-omics analysis explores the effect of chronic exercise on liver metabolic reprogramming in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229755 | GEO | 2023/07/12
REPOSITORIES: GEO
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Project description:Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The presented study conducted a microarray on hippocampal samples from adult (3.5 month-old) and aged (18 month-old) male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects. In total 20 samples (4 aged exercise, 4 aged sedentary, 6 adult exercise, and 6 adult sedentary) plus 4 technical replicates (24 total) were analyzed.
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Project description:Physical activity is considered a promising preventive intervention to reduce the risk of developing Alzheimer’s disease (AD). However, the positive effect of exercise therapy has not been proven conclusively yet, likely due to confounding factors such as varying activity regimens and life or disease stages. To examine the impact of different exercise regimens in the early disease stages, we subjected young 5xFAD and wild-type mice to 1-day (acute, 3-month-old) and 30-day (chronic, 2-month-old) voluntary wheel running and compared them with age-matched sedentary controls. We observed a significant increase in brain lactate levels in acutely trained 5xFAD mice relative to all other experimental groups. Subsequent RNA-seq analysis from brain did not reveal major differences in transcriptomic regulation between training durations in 5xFAD mice. In contrast, acute training yielded large gene expression differences in wild-type animals relative to their chronically trained and sedentary counterparts. The comparison of 5xFAD and wild-type mice showed the highest transcriptional differences in the chronic and sedentary groups, whereas acute training was associated with much fewer DEGs. In conclusion, our results suggest that different training durations did not affect the global transcriptome of 3-month-old 5xFAD mice, whereas acute running seemed to induce a similar transcriptional stress state in wild-type animals as already known for 5xFAD mice.
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Project description:Exercise training improves whole body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues including adipose tissue. To determine if exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, nine days post-transplantation, mice receiving trained scWAT had improved glucose tolerance and enhanced insulin sensitivity compared to mice transplanted with sedentary scWAT or sham-treated mice. Mice transplanted with trained scWAT had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat fed recipient mice were transplanted with trained scWAT. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT including increased expression of ∼1550 genes involved in numerous cellular functions, including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis.
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Project description:Exercise improves health and well-being across diverse organ systems, and elucidating mechanisms underlying the beneficial effects of exercise on health can lead to new therapies for disease. We find that exercise training in humans causes profound changes in subcutaneous adipose tissue (scWAT) gene expression, including genes encoding secreted proteins. In addition, we used our previously published microarray dataset derived from scWAT from mice housed in static cages (sedentary controls) or mice housed in cages with running wheels for 11 days. Genes that were significantly changed by exercise training in humans and mice were further selected by annotation for Extracellular Space in Gene Ontology. Of these genes, the most significantly correlated with the total wheel running distance in the trained mice was Tgfb2. We validated that exercise training increased TGFB2 mRNA in scWAT of human subjects using RT-qPCR. This led us to hypothesize that TGF-β2 is an exercise-induced adipokine. To determine the therapeutic potential and mechanism for increased TGF-β2, we investigated mouse models of exercise training and obesity. Our findings indicate that exercise training improves metabolism through inter-organ communication with fat via a TGF-β2 signaling, providing a novel mechanism for counteracting metabolic disease.
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Project description:n total, 16 7-week-old male F344 rats were subjected to model regular exercise and sedentary lifestyle. In the second week after arrival and acclimatization to the reversed light/dark cycle, rats were introduced to the forced running wheel without a specific running mode. It was followed by a 12-day training phase for all 16 experimental animals (started at 9 weeks of age) by gradually increasing the running speed and duration. During the training phase, 8 best performers were selected for the runner group while the remaining 8 rats were assigned to the sedentary group. The regular forced running exercise phase for the runner group lasted for 5 weeks in total, including 4 weeks of regular running. After 4 weeks of regular exercise, rats underwent brief anesthesia and of blood from the tail vein were taken. This step was repeated for the same animals immediately after 1h of running. On the same day, a blood sample was collected from the sedentary rats following the same protocol. Plasma was collected and immediately frozen for further EV isolation. EVs were isolated from rat plasma by size exclusion chromatography. RNA libraries were constructed using CleanTag® Small RNA Library Prep Kit (Trilink Biotechnologies, USA) and sequenced on Illumina NextSeq500 instrument using NextSeq 500/550 Mid Output Kit v2.5 (150 cycles).
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