Daidzein Inhibits Muscle Atrophy by Suppressing Inflammatory Cytokine- and Muscle Atrophy-Related Gene Expression
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-i...
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Published in: | Nutrients Vol. 16; no. 18; p. 3084 |
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Abstract | 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. |
---|---|
AbstractList | Background: 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. Methods: 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. Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 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 (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy. Background: 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. Methods: 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. Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group ( Fbxo32 , p = 0.0012; Trim63 , p < 0.0001; Foxo1 , p < 0.0001; Tnfa , p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 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 ( Tnfa , p = 0.0201; Il6 , p = 0.0008; Fbxo32 , p < 0.0001; Hdac4 , p = 0.0002; Trim63 , p = 0.0114; Foxo1 , p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells ( Foxo1 , p = 0.0078; MuRF1, p = 0.0119). Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy. 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.BACKGROUNDSarcopenic 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.METHODSTo 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 (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 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 (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119).RESULTSThe isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 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 (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119).The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.CONCLUSIONSThe daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy. 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. |
Audience | Academic |
Author | Nakanishi, Naoko Kobayashi, Ayaka Kitagawa, Nobuko Okamura, Takuro Senmaru, Takafumi Ushigome, Emi Munekawa, Chihiro Fukui, Michiaki Majima, Saori Kawai, Sayaka Hamaguchi, Masahide River, Budau Nakajima, Hanako Okada, Hiroshi |
AuthorAffiliation | Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; c-mori@koto.kpu-m.ac.jp (C.M.) |
AuthorAffiliation_xml | – name: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; c-mori@koto.kpu-m.ac.jp (C.M.) |
Author_xml | – sequence: 1 givenname: Chihiro orcidid: 0000-0001-9603-1802 surname: Munekawa fullname: Munekawa, Chihiro organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 2 givenname: Takuro orcidid: 0000-0001-7269-1697 surname: Okamura fullname: Okamura, Takuro organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 3 givenname: Saori surname: Majima fullname: Majima, Saori organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 4 givenname: Budau surname: River fullname: River, Budau organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 5 givenname: Sayaka orcidid: 0009-0009-2984-5094 surname: Kawai fullname: Kawai, Sayaka organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 6 givenname: Ayaka surname: Kobayashi fullname: Kobayashi, Ayaka organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 7 givenname: Hanako orcidid: 0000-0002-3209-1790 surname: Nakajima fullname: Nakajima, Hanako organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 8 givenname: Nobuko surname: Kitagawa fullname: Kitagawa, Nobuko organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 9 givenname: Hiroshi orcidid: 0000-0002-1707-970X surname: Okada fullname: Okada, Hiroshi organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 10 givenname: Takafumi surname: Senmaru fullname: Senmaru, Takafumi organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 11 givenname: Emi orcidid: 0000-0003-1031-4380 surname: Ushigome fullname: Ushigome, Emi organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 12 givenname: Naoko surname: Nakanishi fullname: Nakanishi, Naoko organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 13 givenname: Masahide orcidid: 0000-0002-8651-4445 surname: Hamaguchi fullname: Hamaguchi, Masahide organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan – sequence: 14 givenname: Michiaki orcidid: 0000-0003-0903-1797 surname: Fukui fullname: Fukui, Michiaki organization: Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan |
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Keywords | daidzein high-sucrose diet C2C12 myotubes high-fat diet muscle atrophy sarcopenic obesity mice soy isoflavones sarcopenia |
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SubjectTerms | 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 |
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Title | Daidzein Inhibits Muscle Atrophy by Suppressing Inflammatory Cytokine- and Muscle Atrophy-Related Gene Expression |
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