β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.

Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β-hydroxy β-methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethason...

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Main Authors: Kyung Kyun Noh, Ki Wung Chung, Yeon Ja Choi, Min Hi Park, Eun Ji Jang, Chan Hum Park, Changshin Yoon, Nam Deuk Kim, Mi Kyung Kim, Hae Young Chung
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4102592?pdf=render
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author Kyung Kyun Noh
Ki Wung Chung
Yeon Ja Choi
Min Hi Park
Eun Ji Jang
Chan Hum Park
Changshin Yoon
Nam Deuk Kim
Mi Kyung Kim
Hae Young Chung
author_facet Kyung Kyun Noh
Ki Wung Chung
Yeon Ja Choi
Min Hi Park
Eun Ji Jang
Chan Hum Park
Changshin Yoon
Nam Deuk Kim
Mi Kyung Kim
Hae Young Chung
author_sort Kyung Kyun Noh
collection DOAJ
description Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β-hydroxy β-methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy.
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spelling doaj.art-e9ed6be5cd524e4bab26339b6660c36d2022-12-21T23:27:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10294710.1371/journal.pone.0102947β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.Kyung Kyun NohKi Wung ChungYeon Ja ChoiMin Hi ParkEun Ji JangChan Hum ParkChangshin YoonNam Deuk KimMi Kyung KimHae Young ChungSkeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β-hydroxy β-methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy.http://europepmc.org/articles/PMC4102592?pdf=render
spellingShingle Kyung Kyun Noh
Ki Wung Chung
Yeon Ja Choi
Min Hi Park
Eun Ji Jang
Chan Hum Park
Changshin Yoon
Nam Deuk Kim
Mi Kyung Kim
Hae Young Chung
β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
PLoS ONE
title β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
title_full β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
title_fullStr β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
title_full_unstemmed β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
title_short β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
title_sort β hydroxy β methylbutyrate improves dexamethasone induced muscle atrophy by modulating the muscle degradation pathway in sd rat
url http://europepmc.org/articles/PMC4102592?pdf=render
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