Background/Objectives: Ovariectomized rodents experience metabolic dysfunction in whole-body and skeletal muscle. A disrupted balance between oxidative stress and antioxidants might exacerbate metabolic dysfunction in ovariectomized rodents. Dietary antioxidants, such as vitamin E intake, before or during exercise would be beneficial by mitigating the exercise-induced increase in oxidative stress in ovariectomized rodents. The purpose of the current study was to investigate the potential effect of vitamin E intake combined with voluntary exercise on whole-body and skeletal muscle metabolism in ovariectomized mice. Methods: This study used C57BL/6J wild-type female mice (n = 40, 8 weeks old), which were randomly assigned into sham (SHM), ovariectomy (OVX), ovariectomy with exercise (OVXVE), ovariectomy with vitamin E (OVXV), ovariectomy with exercise and vitamin E (OVXVE) groups. Body composition, resting metabolic rate, glucose tolerance, skeletal muscle mitochondrial function, and protein contents were assessed using dual-energy x-ray absorptiometry, indirect calorimetry, glucose tolerance test, O₂K OROBOROS, and Western blot, respectively. Results: The combined treatment of vitamin E and voluntary wheel running did not show a beneficial effect on whole-body metabolism such as fat mass, energy expenditure, and glucose tolerance. However, independent of exercise intervention, vitamin E intake enhanced mitochondrial function, Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-a), and adenosine monophosphate-activated protein kinase (AMPK) levels and also reduced oxidative stress in the skeletal muscles of ovariectomized mice. Specifically, in the soleus muscle, vitamin E intake enhanced mitochondrial function and PGC1-a content (p < 0.05). In the gastrocnemius muscle, vitamin E intake enhanced PGC1-a and AMPK levels and reduced a marker of oxidative stress (p < 0.05). Conclusions: Vitamin E, as a potent antioxidant, may play a crucial role in maintaining skeletal muscle health in ovariectomized mice. More studies are necessary to investigate whether this finding is applicable to women.

PURPOSE: A correlation exists between a healthy physiological state and the diversity of the gut microbiome. Menopause-induced deterioration of whole-body metabolism negatively contributes to microbial diversity. The combined effect of acetic acid supplementation and exercise on the gut microbiome remains unknown. This study aimed to investigate 1) whether menopause negatively influences gut microbial diversity, including Firmicutes abundance, and 2) whether the combined treatment of acetic acid supplementation and exercise rescues microbial dysbiosis, and which specific bacteria are related to this rescue effect.METHODS: The 15-week study used 8-week-old female C57BL/6J wild-type mice (n=40), which were randomly assigned to sham (SHM), ovariectomy (OVX), ovariectomy with exercise (OVXE), ovariectomy with acetic acid (OVXA), or ovariectomy with exercise and acetic acid (OVXAE) groups. Gut microbial diversity and abundance were assessed using next-generation sequencing (NGS).RESULTS: Firmicutes were more abundant in the OVX group than in the SHM group. However, OVXA partially protected against the OVX-induced increase in Firmicutes (SHM, 50.6%; OVX, 57.2%; OVXE, 52.0%; OVXA, 50.6%; and OVXAE, 56.5%). In terms of microbial diversity, the acetic acid-supplemented groups (OVXA and OVXAE) showed greater microbial diversity than the SHM and OVX groups (p<.05). The phylogenetic cladogram analysis showed that the OVXA and OVXAE groups had lower levels of UCG009 and Akkermansia (p<.05) than the OVX group.CONCLUSIONS: Ovariectomy increased the relative abundance of Firmicutes. Acetic acid supplementation partially attenuated the increased proportion of Firmicutes in ovariectomized mice. Notably, this study found that acetic acid supplementation showed a significant beneficial effect on microbial diversity in ovariectomized mice, independent of exercise intervention. Future research should explore the potential role of UCG009 in protecting against menopause-related metabolic dysfunction.

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.