The Effect of High Glucocorticoid Administration and Food Restriction on Rodent Skeletal Muscle Mitochondrial Function and Protein Metabolism

Abstract

BackgroundGlucocorticoids 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 FindingsWe 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/SignificanceMPred 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.

Sclerostin antibody and interval treadmill training effects in a rodent model of glucocorticoid-induced osteopenia

“…Consistent with the data obtained by others in rat models treated with GCs [53,54] we observed significantly lower weight gain (-10%) with methylprednisolone treatment due to lower lean mass gain, and resulting in higher percentage of fat mass [55,56]. As expected, GC administration resulted in failure to accrue bone during continued skeletal growth as reflected in DXA BMC and BMD.…”

A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration

“…Our data of ZOL reversion of BAP alteration induced by GC supports the bone formation activity of zoledronic acid and its use in this condition. Reinforcing this finding, the reduced ponderal growth in animals treated with GC is probably not due solely to the catabolic effect in muscle [49,50], but also to a direct effect in bone mass [30] that was improved by ZOL.…”

Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: central actor and therapeutic target

“…Decreased state 3 respiration has also been reported in isolated mitochondria from rat skeletal muscle (Martens et al 1991). In contrast, changes in COX activity in this same tissue have been shown to vary according to available studies (Weber et al 2002; Duclos et al 2004; You et al 2009), while being enhanced in C2C12 myotubes exposed to dexamethasone (1 μ m ) for 3 days (Weber et al 2002). In addition, there is evidence that the type of corticosteroid also influences the effect on muscle.…”

“…In animals, corticosteroids can diminish both whole body weight and muscle weight (Koerts‐de Lang et al 1999; You et al 2009), whereas their effect on mitochondrial number and function appear to be inconstant. In rat skeletal muscle, Koerts‐de Lang et al (1999) and You et al (2009) found no decrease in CS activity, whereas Duclos et al (2004) reported a drop in activity following high‐dose administration of corticosterone. Decreased state 3 respiration has also been reported in isolated mitochondria from rat skeletal muscle (Martens et al 1991).…”