Effect of Isoflavone on Muscle Atrophy in Ovariectomized Mice
Sayaka Kawai1, Takuro Okamura1, Chihiro Munekawa1
1Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Background:
Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD).
Methods:
At 7 weeks old, female C57BL6/J mice (18-20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT-PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed.
Results:
The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones.
Conclusions:
Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women.
Insights
Isoflavone intake improved muscle strength in mice by altering gut microbiota, offering potential benefits for sarcopenia in menopausal women. This study highlights a novel therapeutic avenue for age-related muscle decline.
Area of Science:
- Muscle physiology and aging research
- Nutritional science and dietary interventions
- Gut microbiome and host interactions
Background:
- Sarcopenia, a decline in muscle mass, is worsened by postmenopausal estrogen reduction.
- Isoflavones, plant compounds with estrogenic activity, may mitigate metabolic disorders.
- This study investigates isoflavone effects on ovariectomized mice on a high-fat, high-sucrose diet.
Purpose of the Study:
- To assess the impact of isoflavone supplementation on metabolic health and muscle function.
- To explore changes in skeletal muscle gene expression and gut microbiota composition.
- To determine the potential of isoflavones in counteracting sarcopenia-related changes.
Main Methods:
- Ovariectomized (OVX) mice were fed a high-fat, high-sucrose diet, with half receiving isoflavone water.
- Metabolic assessments included glucose and insulin tolerance tests.
- Muscle strength (grip test), gene expression (RT-PCR, NGS), protein levels (Western blot), and gut microbiota (16S rRNA sequencing) were analyzed.
Main Results:
- Isoflavones did not alter body weight, glucose tolerance, or lipid metabolism.
- Isoflavone treatment significantly increased grip strength and altered soleus muscle gene expression (e.g., decreased Trim63).
- Gut microbiota analysis revealed increased Bacteroidetes, decreased Firmicutes, and enhanced diversity; TNF-α and UPR pathways were negatively associated with isoflavones.
Conclusions:
- Isoflavone consumption positively modulates gut microbiota composition and diversity.
- Isoflavones enhance muscle strength, independent of significant metabolic improvements in this model.
- These findings suggest isoflavones may be a promising intervention for sarcopenia in menopausal women.
