The effect of high glucocorticoid administration and food restriction on rodent skeletal muscle mitochondrial function and protein metabolism.

Abstract

BACKGROUND: Glucocorticoids levels are high in catabolic conditions but it is unclear how much of the catabolic effects are due to negative energy balance versus glucocorticoids and whether there are distinct effects on metabolism and functions of specific muscle proteins. METHODOLOGY/PRINCIPAL FINDINGS: We determined whether 14 days of high dose methylprednisolone (MPred, 4 mg/kg/d) Vs food restriction (FR, food intake matched to MPred) in rats had different effects on muscle mitochondrial function and protein fractional synthesis rates (FSR). Lower weight loss (15%) occurred in FR than in MPred (30%) rats, while a 15% increase occurred saline-treated Controls. The per cent muscle loss was significantly greater for MPred than FR. Mitochondrial protein FSR in MPred rats was lower in soleus (51 and 43%, respectively) and plantaris (25 and 55%) than in FR, while similar decline in protein FSR of the mixed, sarcoplasmic, and myosin heavy chain occurred. Mitochondrial enzymatic activity and ATP production were unchanged in soleus while in plantaris cytochrome c oxidase activity was lower in FR than Control, and ATP production rate with pyruvate + malate in MPred plantaris was 28% lower in MPred. Branched-chain amino acid catabolic enzyme activities were higher in both FR and MPred rats indicating enhanced amino acid oxidation capacity. CONCLUSION/SIGNIFICANCE: MPred and FR had little impact on mitochondrial function but reduction in muscle protein synthesis occurred in MPred that could be explained on the basis of reduced food intake. A greater decline in proteolysis may explain lesser muscle loss in FR than in MPred rats.