Daidzein Inhibits Muscle Atrophy by Suppressing Inflammatory Cytokine- and Muscle Atrophy-Related Gene Expression

• Published in: Nutrients Vol. 16; no. 18; p. 3084
• Main Authors: Munekawa, Chihiro, Okamura, Takuro, Majima, Saori, River, Budau, Kawai, Sayaka, Kobayashi, Ayaka, Nakajima, Hanako, Kitagawa, Nobuko, Okada, Hiroshi, Senmaru, Takafumi, Ushigome, Emi, Nakanishi, Naoko, Hamaguchi, Masahide, Fukui, Michiaki
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-09-2024; MDPI
• Subjects: Animals; Atrophy; C2C12 myotubes; Cell Line; Cholesterol; Cohort analysis; Cytokines; Cytokines - genetics; Cytokines - metabolism; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Enzymes; Feces; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O1 - metabolism; Gene expression; Gene Expression Regulation - drug effects; Genes; Glucose; Glycine max - chemistry; high-fat diet; high-sucrose diet; Isoflavones; Isoflavones - pharmacology; Male; Medical equipment and supplies industry; Medical test kit industry; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Atrophy - drug therapy; Muscular Atrophy - metabolism; Muscular Atrophy - prevention & control; Musculoskeletal system; Obesity; Obesity - metabolism; Older people; Palmitic Acid - pharmacology; Pharmaceutical industry; Protein synthesis; Proteins; Resveratrol; Sarcopenia; Sarcopenia - drug therapy; Sarcopenia - metabolism; Sarcopenia - prevention & control; sarcopenic obesity; SKP Cullin F-Box Protein Ligases - genetics; SKP Cullin F-Box Protein Ligases - metabolism; Statistical analysis; Tripartite Motif Proteins - genetics; Tripartite Motif Proteins - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; France; United Kingdom; Japan; daidzein; high-sucrose diet; C2C12 myotubes; high-fat diet; muscle atrophy; sarcopenic obesity; mice; soy isoflavones; sarcopenia
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16183084

Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects.
To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro.
The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (
,
= 0.0012;
,
< 0.0001;
,
< 0.0001;
,
= 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces,
0.0122; muscle,
0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (
,
0.0201;
,
0.0008;
,
0.0001;
,
0.0002;
,
0.0114;
,
0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (
,
0.0078; MuRF1,
0.0119).
The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.