Background: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. Methods: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. Results: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. Conclusion: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Background: High-altitude hypoxia is known to adversely affect bone health, leading to accelerated bone loss and metabolic alterations. Recent studies suggest that factors such as bicarbonate and gut microbiota may play key roles in bone health. Mineral water, rich in bicarbonate, may influence bone health and the gut–bone axis under such conditions. Methods: Mice were exposed to hypoxia and treated with different concentrations of drinking water. Bone-related parameters were assessed using dual-energy X-ray absorptiometry (DXA) and Micro-CT. Bone health was assessed using the measurement of serum biomarkers. Additionally, Untargeted Metabolomics was employed to analyze differential metabolites between groups, while gut microbiota composition was analyzed using 16S rRNA sequencing. Results: BMW consumption increased bone mineral density (BMD) and helped alleviate the damage to the microstructure of bones caused by hypoxia and delayed the progression of osteoporosis. Additionally, BMW was shown to enhance probiotics such as Akkermansia and Dubosiella and regulate the longevity-regulating pathway as well as the PI3K/AKT/mTOR (PAM) signaling pathway. This study also discovered changes in metabolic products due to BMW intervention, predominantly in pathways such as the amino acid, prostaglandin, and purine metabolisms, with correlation analysis further exploring the relationships between gut microbiota and these differential metabolites. Conclusions: Long-term exposure to high-altitude hypoxic conditions affects the structure of gut microbiota and bone metabolism in mice. The consumption of BMW improves the structure of gut microbiota and regulates the metabolic pathways to maintain bone health under high-altitude hypoxia.