Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats

Abstract

Aged rats are more sensitive to injury, possibly through an impairment of nitrogen and glutamine (Gln) metabolisms mediated by glucocorticoids. We studied the metabolic kinetic response of adult and old rats during glucocorticoid treatment. The male Sprague-Dawley rats were 24 or 3 mo old. Both adult and old rats were divided into 7 groups. Groups labeled G3, G5, and G7 received, by intraperitoneal injection, 1.50 mg/kg of dexamethasone (Dex) for 3, 5, and 7 days, respectively. Groups labeled G3PF, G5PF, and G7PF were pair fed to the G3, G5, or G7 groups and were injected with an isovolumic solution of NaCl. One control group comprised healthy rats fed ad libitum. The response to aggression induced specifically by Dex (i.e., allowing for variations in pair-fed controls) appeared later in the aged rats (decrease in nitrogen balance from day 1 in adults but only from day 4 in old rats). The adult rats rapidly adapted to Dex treatment, whereas the catabolic state worsened until the end of treatment in the old rats. Gln homeostasis was not maintained in the aged rats; despite an early increase in muscular Gln synthetase activity, the Gln pool was depleted. These results suggest a kinetic impairment of both nitrogen and muscle Gln metabolisms in response to Dex with aging.

Does Glutamine Supplementation Decrease the Response of Muscle Glutamine Synthesis to Fasting in Muscle in Adult and Very Old Rats?

“…GS activity was increased by a factor of 1.5-to 2-fold in 25-27-month rats and may be a consequence of aging-induced stress. This GS activity stimulation, observed in both female and male rats, was similar to that in aging (6 -24 months) in catabolic states (such as glucocorticoid treatment 10,15 or fasting 9 ).…”

Age and aerobic exercise training effects on whole body and muscle protein metabolism

“…This is an important issue, because protein turnover is necessary to maintain tissue quality by continuous replacement of damaged proteins. Older people may accumulate a greater number of damaged or modified proteins that contribute to the reduction in body functions, which could result in slower tissue repair in response to illness or trauma (21). Interventions that Fig.…”

Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment

“…Glucocorticoid treatment, particularly with dexamethasone, induces a hypercatabolic state characterized by accelerated protein turnover in skeletal muscle and gluconeogenesis in the liver, leading finally to augmented energy expenditure. Indeed, dexamethasone administration in healthy humans is associated with an increase in the resting energy expenditure (5,16,22,29), which corresponds to a higher oxygen consumption at the whole body level. We have suggested that the increased energy expenditure may be linked to the effect of glucocorticoids on mitochondria (8,27,28).…”