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Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

Nishida H, Ikegami A, Kaneko C, Kakuma H, Nishi H, Tanaka N, Aoyama M, Usami M, Okimura Y - PLoS ONE (2015)

Bottom Line: BCAA did not decrease the mRNA level of atrogin-1 or MuRF1.BCAA prevented the Dex-induced decrease in CSA.BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.

ABSTRACT
Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR) mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

No MeSH data available.


Related in: MedlinePlus

Effect of BCAA and Dex administration on body weight, food intake and muscle mass in the GH-treated SDRs.A. Dex treatment for 5 days elicited a reduction in body weight gain in the GH-administered SDRs irrespective of BCAA administration. BCAA did not increase body weight gain. B. Food intake by the Dex-treated SDRs was decreased irrespective of BCAA administration. C. Dex reduced soleus muscle mass, and BCAA recovered this reduction. D. Dex reduced EDL muscle mass, but BCAA did not recover this reduction. *, P < 0.05 vs. control group.
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pone.0128805.g005: Effect of BCAA and Dex administration on body weight, food intake and muscle mass in the GH-treated SDRs.A. Dex treatment for 5 days elicited a reduction in body weight gain in the GH-administered SDRs irrespective of BCAA administration. BCAA did not increase body weight gain. B. Food intake by the Dex-treated SDRs was decreased irrespective of BCAA administration. C. Dex reduced soleus muscle mass, and BCAA recovered this reduction. D. Dex reduced EDL muscle mass, but BCAA did not recover this reduction. *, P < 0.05 vs. control group.

Mentions: To examine the effect of GH on SDR muscles, we administered GH to the SDRs using osmotic pumps. GH increased the body weights of SDRs in experiment 2 compared to the SDRs that did not receive GH in experiment 1 (control; 58.1 ± 2.1 g, GH/control; 98.8 ± 2.6 g, at 8 weeks). However, Dex administration for 5 days elicited a reduction in body weight gain in the GH-treated SDRs irrespective of the administration of BCAA (body weight of GH/control; 98.8 ± 2.6 g, GH/Dex; 88.4 ± 0.7 g, GH/Dex + BCAA; 87.8 ± 1.0 g at 8 weeks). BCAA did not increase body weight gain (Fig 5A). Dex decreased food intake irrespective of BCAA administration (Fig 5B). Although Dex decreased the soleus muscle weights, BCAA reversed this decrease (Fig 5C). Dex decreased the EDL muscle weights in the presence and absence of BCAA (Fig 5D).


Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

Nishida H, Ikegami A, Kaneko C, Kakuma H, Nishi H, Tanaka N, Aoyama M, Usami M, Okimura Y - PLoS ONE (2015)

Effect of BCAA and Dex administration on body weight, food intake and muscle mass in the GH-treated SDRs.A. Dex treatment for 5 days elicited a reduction in body weight gain in the GH-administered SDRs irrespective of BCAA administration. BCAA did not increase body weight gain. B. Food intake by the Dex-treated SDRs was decreased irrespective of BCAA administration. C. Dex reduced soleus muscle mass, and BCAA recovered this reduction. D. Dex reduced EDL muscle mass, but BCAA did not recover this reduction. *, P < 0.05 vs. control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472719&req=5

pone.0128805.g005: Effect of BCAA and Dex administration on body weight, food intake and muscle mass in the GH-treated SDRs.A. Dex treatment for 5 days elicited a reduction in body weight gain in the GH-administered SDRs irrespective of BCAA administration. BCAA did not increase body weight gain. B. Food intake by the Dex-treated SDRs was decreased irrespective of BCAA administration. C. Dex reduced soleus muscle mass, and BCAA recovered this reduction. D. Dex reduced EDL muscle mass, but BCAA did not recover this reduction. *, P < 0.05 vs. control group.
Mentions: To examine the effect of GH on SDR muscles, we administered GH to the SDRs using osmotic pumps. GH increased the body weights of SDRs in experiment 2 compared to the SDRs that did not receive GH in experiment 1 (control; 58.1 ± 2.1 g, GH/control; 98.8 ± 2.6 g, at 8 weeks). However, Dex administration for 5 days elicited a reduction in body weight gain in the GH-treated SDRs irrespective of the administration of BCAA (body weight of GH/control; 98.8 ± 2.6 g, GH/Dex; 88.4 ± 0.7 g, GH/Dex + BCAA; 87.8 ± 1.0 g at 8 weeks). BCAA did not increase body weight gain (Fig 5A). Dex decreased food intake irrespective of BCAA administration (Fig 5B). Although Dex decreased the soleus muscle weights, BCAA reversed this decrease (Fig 5C). Dex decreased the EDL muscle weights in the presence and absence of BCAA (Fig 5D).

Bottom Line: BCAA did not decrease the mRNA level of atrogin-1 or MuRF1.BCAA prevented the Dex-induced decrease in CSA.BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.

ABSTRACT
Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR) mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

No MeSH data available.


Related in: MedlinePlus