Dietary Genistein Prevents Denervation-Induced Muscle Atrophy in Male Rodents via Effects on Estrogen Receptor-α

Shinya Aoyama,Huijuan Jia,Kyoko Nakazawa,Junki Yamamura,Kenji Saito,Hisanori Kato

doi:10.3945/jn.115.226316

Abstract

Background: Genistein has high estrogenic activity. Previous studies have shown beneficial effects of estrogen or hormone replacement therapy on muscle mass and muscle atrophy.Objective: We investigated the preventive effects and underlying mechanisms of genistein on muscle atrophy.Methods: In Expt. 1, male Wistar rats were fed a diet containing no genistein [control (CON)] or 0.05% genistein (GEN; wt:wt diet) for 24 d. On day 14, the sciatic nerve in the left hind leg was severed, and the right hind leg was sham-treated. In Expt. 2, male C57BL6J mice were subcutaneously administered a vehicle (Veh group) or the estrogen receptor (ER) antagonist ICI 182,780 (ICI group) via an osmotic pump for 27 d, and each group was subsequently fed CON or GEN diets from day 3 to day 27. Muscle atrophy was induced on day 17 as in Expt. 1. In Expt. 3, male C57BL6J mice were subcutaneously administered vehicle or a selective ER agonist—ER-α [4,4′,4′-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT)] or ER-β [2,3-bis(4-hydroxyphenyl)-propionitrile (DPN)]—or genistein (GEN-sc-i) via an osmotic pump for 13 d, and muscle atrophy was induced on day 3 as in Expt. 1. The ratio of denervated soleus muscle weight to sham-operated soleus muscle weight (d/s ratio) was used as the index of muscle atrophy.Results: Expt. 1: The d/s ratio in the GEN group was 20% higher than that in the CON group (P < 0.05). Expt. 2: The d/s ratio in the Veh-GEN group was 14% higher than that in the Veh-CON group (P < 0.05), although there was no significant difference between ICI-CON and ICI-GEN groups (P = 0.69). Expt. 3: The d/s ratio in the PPT-treated group was 20% greater than that in the Veh group (P < 0.05), but DPN and GEN-sc-i had no effect on the d/s ratio (P ≥ 0.05 compared with vehicle).Conclusion: Genistein intake mitigated denervation-induced soleus muscle atrophy. ER-α was related to the preventive effect of genistein on muscle atrophy.

Highlights

The maintenance of skeletal muscle mass is regulated by the balance between muscle protein synthesis and degradation
The expressions of Atrogin1 and Murf1 in the soleus muscle in the CON group were significantly increased by denervation (P = 0.014 and 0.021, respectively), whereas those in the GEN group were not significantly increased by denervation (P = 0.48 and 0.21, respectively) (Figure 1C, D)
Hormone replacement therapy has been shown to have positive effects on muscle mass retention in aging women [10]. These reports indicated that some flavonoids, such as isoflavones, with estrogenic activity may have a preventive effect on muscle atrophy

Summary

Introduction

The maintenance of skeletal muscle mass is regulated by the balance between muscle protein synthesis and degradation. Skeletal muscle atrophy occurs as a result of enhanced protein degradation, which can be induced by several factors, including low mechanical stress, fasting, steroid treatment, cachexia, and excess oxidative stress. Objective: We investigated the preventive effects and underlying mechanisms of genistein on muscle atrophy. 2, male C57BL6J mice were subcutaneously administered a vehicle (Veh group) or the estrogen receptor (ER) antagonist ICI 182,780 (ICI group) via an osmotic pump for 27 d, and each group was subsequently fed CON or GEN diets from day 3 to day 27. Muscle atrophy was induced on day 17 as in Expt. 3, male C57BL6J mice were subcutaneously administered vehicle or a selective ER agonist—ER-a [4,4#,4#-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT)] or ER-b [2,3-bis(4-hydroxyphenyl)-propionitrile (DPN)]—or genistein (GEN-sc-i) via an osmotic pump for 13 d, and muscle atrophy was induced on day 3 as in Expt.

Objectives

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Results

Conclusion