Obesity is a common metabolic disorder caused by a sedentary lifestyle, and a high-fat and a high-glucose diet in the form of fast foods. High-fat diet-induced obesity is a major cause of diabetes and cardiovascular diseases, whereas exercise and physical activity can ameliorate these disorders. Moreover, exercise and the gut microbiota are known to be interconnected, since exercise can increase the gut microbial diversity and contribute to the beneficial health effects. In this context, we analyzed the effect of diet and exercise on the gut microbiota of mice, by next-generation sequencing of the bacterial V4 region of 16S rRNA. Briefly, mice were divided into four groups: chow-diet (CD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise-only (EX). The mice underwent treadmill exercise and diet intervention for 8 weeks, followed by the collection of their feces and DNA extraction for sequencing. The data were analyzed using the QIIME 2 bioinformatics platform and R software to assess their gut microbial composition, richness, and diversity. The Bacteroidetes to Firmicutes ratio was found to be decreased manifold in the HFD and HFX groups compared to the CD and EX groups. The gut microbial richness was comparatively lower in the HFD and HFX groups and higher in the CD and EX groups (ACE, Chao1, and observed OTUs). However, the Shannon alpha diversity index was higher in the HFD and HFX groups than in the CD and EX groups. The beta diversity based on Jaccard, Bray–Curtis, and weighted UniFrac distance metrics was significant among the groups, as measured by PERMANOVA. Paraprevotella, Desulfovibrio, and Lactococcus were the differentially abundant/present genera based on the intervention groups and in addition to these three bacteria, Butyricimonas and Desulfovibrio C21c20 were differentially abundant/present based on diet. Hence, diet significantly contributed to the majority of the changes in the gut microbiota.

Regular exercise provides several health benefits that can improve the cardiovascular and musculoskeletal systems, but clear evidence on the effect of exercise-induced hyperventilation in particulate matter (PM) exposure is still lacking. This study aimed to investigate the effects of exercise in PM exposure on reactive oxygen species (ROS) generation, inflammatory response, and mitochondrial integrity in human lung epithelial cells (A549), as well as in mouse lung tissue. In in vitro experiments, PM treatment was shown to significantly increased ROS production, and reduced cell viability and mitochondrial function in A549 cells. The mice were divided into four groups for an in vivo exercise experiment: control (CON), PM inhalation (PI), PM inhalation during exercise (PIE), and exercise (EX) groups. The PI and PIE groups were exposed to 100 μg/m³ of PM for 1 h per day for a week. The PIE and EX groups performed treadmill exercises every day for 1 h at 20 m/min for a week. The levels of pro-inflammatory markers (IL-6 and TNF-α) were significantly higher in the PI group than in the CON group (P < 0.001 and P < 0.01, respectively). The carbonyl protein level was decreased in EX vs. PI (P < 0.001). Mitochondrial fission (Drp1) content was significantly decreased in the EX vs. CON group (P < 0.01), but anti-mitochondrial fission (P-Drp1 Ser637) was increased in the EX vs. PI group (P < 0.05). Mitochondrial autophagy (mitophagy), which is an assessment of mitochondrial integrity, was markedly increased in PI vs. CON (P < 0.001), but the level was reversed in PIE (P < 0.05). Lung fibrosis was increased in PI vs. CON group (P < 0.001), however, the cells were rescued in the PIE (P < 0.001). The number of apoptotic cells was remarkably increased in the PI vs. CON group (P < 0.001), whereas the level was decreased in the PIE (P < 0.001). Taken together, these results showed that short-term exposure to PM triggers oxidative stress, pro-inflammatory responses, and apoptosis in the lungs, but the PM-induced adverse effects on the lung tissue are not exacerbated by exercise-induced PM hyperventilation but rather has a protective effect.

Particulate matter (PM) has deleterious consequences not only on the respiratory system but also on essential human organs, such as the heart, blood vessels, kidneys, and liver. However, the effects of PM inhalation on skeletal muscles have yet to be sufficiently elucidated. Female C57BL/6 or mt-Keima transgenic mice were randomly assigned to one of the following four groups: control (CON), PM exposure alone (PM), treadmill exercise (EX), or PM exposure and exercise (PME). Mice in the three-treatment group were subjected to treadmill running (20 m/min, 90 min/day for 1 week) and/or exposure to PM (100 μg/m³). The PM was found to exacerbate oxidative stress and inflammation, both at rest and during exercise, as assessed by the levels of proinflammatory cytokines, manganese-superoxide dismutase activity, and the glutathione/oxidized glutathione ratio. Furthermore, we detected significant increases in the levels of in vivo mitophagy, particularly in the PM group. Compared with the EX group, a significant reduction in the level of mitochondrial DNA was recorded in the PME group. Moreover, PM resulted in a reduction in cytochrome c oxidase activity and an increase in hydrogen peroxide generation. However, exposure to PM had no significant effect on mitochondrial respiration. Collectively, our findings in this study indicate that PM has adverse effects concerning both oxidative stress and inflammatory responses in skeletal muscle and mitochondria, both at rest and during exercise.

Inhalation of ambient particulate matter (PM) can disrupt the gut microbiome, while exercise independently influences the gut microbiome by promoting beneficial bacteria. In this study, we analyzed changes in gut microbial diversity and composition in response to combined interventions of PM exposure and aerobic exercise, extending up to 12 weeks. This investigation was conducted using mice, categorized into five groups: control group (Con), exercise group (EXE), exercise group followed by 3-day exposure to PM (EXE + 3-day PM), particulate matter exposure (PM), and PM exposure with concurrent treadmill exercise (PME). Notably, the PM group exhibited markedly lower alpha diversity and richness compared to the Con group and our analysis of beta diversity revealed significant variations among the intervention groups. Members of the Lachnospiraceae family showed significant enhancement in the exercise intervention groups (EXE and PME) compared to the Con and PM groups. The biomarker Lactobacillus, Coriobacteraceae, and Anaerofustis were enriched in the EXE group, while Desulfovibrionaceae, Mucispirillum schaedleri, Lactococcus and Anaeroplasma were highly enriched in the PM group. Differential abundance analysis revealed that Paraprevotella, Bacteroides, and Blautia were less abundant in the 12-week PM exposure group than in the 3-day PM exposure group. Moreover, both the 3-day and 12-week PM exposure groups exhibited a reduced relative abundance of Bacteroides uniformis, SMB53, and Staphylococcus compared to non-PM exposure groups. These findings will help delineate the possible roles and associations of altered microbiota resulting from the studied interventions, paving the way for future mechanistic research.

Nonalcoholic fatty liver disease (NALFD), characterized by an abnormal accumulation of triglycerides in hepatocytes, is closely linked to insulin resistance, metabolic syndrome, and changes in lipogenesis in the liver. The accumulation of hepatic lipids can lead to a range of pathologies from mild steatosis to severe cirrhosis. Endurance exercise is known to ameliorate the adverse health effects of NAFLD. Therefore, we aimed to investigate the effect of voluntary wheel running (VWR) on the metabolic changes in the livers of high-fat diet (HFD)-induced NAFLD mice and used LC-MS/MS (Liquid chromatography–mass spectrometry) to determine whether the tested intervention affected the protein expression profiles of the mouse livers. Male C57BL/6 mice were randomly divided into three groups: control (CON), high-fat diet sedentary group (HFD), high-fat diet VWR group (HFX). HFX group performed voluntary wheel running into individually cages, given a high-fat diet for 12 weeks. Food consumption, body weight, and running distance were measured every week. Using 2D (2-dimensional)-gel electrophoresis, we detected and quantitatively analyzed the protein expression with >2.0-fold change in the livers of HFD-fed mice, HFD-fed exercise (HFX) mice, and chow-fed mice. Body weight was significantly increased in HFD compared to CON (P < 0.05). The 2D-gel electrophoresis analysis indicated that there was a difference between CON and HFD groups, showing 31 increased and 27 decreased spots in the total 302 paired spots in the HFD group compared to CON. The analysis showed 43 increased and 17 decreased spots in the total 258 spots in the HFX group compared to CON. Moreover, 12 weeks of VWR showed an increase of 35 and a decrease of 8 spots in a total of 264 paired spots between HFD and HFX. LC-MS/MS of HFD group revealed that proteins involved in ketogenesis, lipid metabolism, and the metabolism of drugs and xenobiotics were upregulated, whereas detoxifying proteins, mitochondrial precursors, transport proteins, proteasomes, and proteins involved in amino acid metabolism were downregulated. On the other hand, VWR counteracted the protein expression profile of HFD-fed mice by upregulating molecular chaperones, gluconeogenesis-, detoxification-, proteasome-, and energy metabolism-related proteins. This study provided a molecular understanding of the HFD- and exercise-induced protein marker expression and presented the beneficial effects of exercise during pathophysiological conditions.

Background: Estrogen deficiency following human menopause or rodent ovariectomy (OVX) induces adverse alterations in body composition and metabolic function. This study investigated the combined effects of acetic acid supplementation and voluntary exercise on metabolic health and skeletal muscle mitochondrial function using an OVX mouse model. Methods: Forty female C57BL/6J mice (8 weeks old) were randomly assigned to 5 groups: sham (SHM), ovariectomized control (OVX), OVX with exercise (OVX-E), OVX with acetic acid (OVX-A), and OVX with both interventions (OVX-AE). Following a 1-week recovery from OVX, a 13-week intervention was initiated: 5% sodium acetate-supplemented chow and/or voluntary wheel running. Body composition, glucose tolerance, total energy expenditure, skeletal muscle mitochondrial function, and the contents of AMPKα, PGC-1α, and carbonyl protein were assessed. Results: OVX impaired whole-body metabolism and skeletal muscle mitochondrial function, specifically in the gastrocnemius muscle. While the exercise alone failed to mitigate the OVX-induced mitochondrial dysfunction, the combined treatment of exercise and acetic acid supplementation significantly rescued from the OVX-induced mitochondrial dysfunction. Conclusions: OVX resulted in detrimental changes in whole-body metabolism, but voluntary exercise and/or acetic acid supplementation had no rescuing effects on those parameters. In gastrocnemius muscle, acetic acid supplementation during exercise enhanced mitochondrial function in OVX mice.