Changes in body composition and dietary intake induced by tumor necrosis factor alpha and corticosterone--individually and in combination.
Previous studies have shown that anorexia and reduced food intake are the main causes of weight loss in rats infused with tumor necrosis factor alpha (TNF-alpha), with no influence on corticosterone concentrations. In contrast, in clinical sepsis, muscle wasting due to increased catabolism is associated with increased corticosteroid concentrations. We hypothesized that in the rat model, corticosterone potentiates the catabolic effect of TNF-alpha in amounts that by itself does not influence muscle catabolism. Orally fed rats were divided into 3 treatment groups: continuous infusion of TNF-alpha (TNF; 100 microg x kg(-1) x d(-1)), corticosterone (Cort; 50 microg x g(-1) x d(-1)), or both (TNF+Cort). Each group was compared with a respective pair-fed (PF) group. In addition an ad libitum (AL)-fed group receiving an infusion of physiologic saline was studied to observe unrestricted food intake and weight gain. After 4 d of infusion, dietary intake and weight gain were significantly higher in the Cort and AL groups than in the TNF and TNF+Cort groups. Although wet liver weights and protein contents were significantly higher in the Cort, TNF, and TNF+Cort groups than in their respective PF group, the TNF and TNF+Cort groups had lower relative carcass weights. The weight and protein content of the diaphragm were lower and nitrogen excretion was higher in the TNF+Cort group than in the respective PF group. The results suggest that TNF-alpha plus corticosterone had a specific catabolic effect on the diaphragm. In addition, together they increased overall nitrogen excretion.
Raina
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Department of Medicine, University of Toronto, Ontario, Canada.
Jeejeebhoy
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KN
D000818:Animals; D001823:Body Composition; D001835:Body Weight; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology; D009584:Nitrogen / Q000652:urine; D009929:Organ Size; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009584:Nitrogen; D003345:Corticosterone