Chronic Inflammation Alters Protein Metabolism in Several Organs of Adult Rats

Abstract

Despite the prevalence of chronic inflammatory diseases in developed countries, few studies have considered the metabolic alterations observed in these disorders. To determine which perturbations in protein metabolism occur during chronic inflammation, and the consequences they have on nutritional requirements, a model of ulcerative colitis was adapted for use in adult rats. Adult Sprague-Dawley male rats (9 mo old) received dextran sulfate sodium (DSS) in their drinking water at 50 g/L for 9 d, then at 20 g/L for 18 d. A group of control rats, matched for age and weight, was pair-fed to the treated rats. DSS induced body weight loss and chronic inflammation characterized by an increase of spleen, liver, ileum and colon weights, of blood leukocytes and acute-phase protein levels. The main inflammatory site was the colon, which presented characteristic histological alterations and increased myeloperoxydase activity. Inflammation was accompanied by oxidative stress, characterized by increased plasma protein carbonyl content and increased liver glutathione concentration, but decreased glutathione concentration in muscle. This DSS-induced colitis led to a stimulation of protein synthesis in spleen (+223%), ileum (+40%) and colon (+63%). By contrast, protein synthesis in muscle slowed down (-23%). In conclusion, like acute inflammation, chronic inflammation induced a stimulation of protein metabolism in several splanchnic organs. In muscle, both protein synthesis and degradation were reduced. Taken together, these data are consistent with inadequate amino acid supply to meet the increased requirement resulting from chronic inflammation.

Mice with experimental colitis show an altered metabolism with decreased metabolic rate

“…has been shown that an acutely induced systemic inflammation results in increased protein catabolism and altered protein synthesis (24,33), showing the importance of inflammation in protein metabolism. Furthermore, chronic inflammation induced by DSS treatment in rats resulted in a stimulation of protein synthesis in various splanchnic organs, i.e., the spleen and intestine, whereas muscle protein turnover was reduced (24).…”

Comparative efficacies of 2 cysteine prodrugs and a glutathione delivery agent in a colitis model

“…However, GSH is not taken up directly by most cell phenotypes and must first be broken down into its component amino acids (cysteine, glutamate, and glycine) by enzymes including δ-glutamyltranspeptidase. 7 Administration of N-acetyl-cysteine in the trinitrobenzene sulfonic acid rat model attenuated this chemically induced colitis, 8 which suggests that GSH precursors may be beneficial in the acute relapse of IBD. Dextran sodium sulfate (DSS) treatment of mice mimics IBD in that it provokes inflammation and macrophage activation, with subsequent loss of epithelial integrity, and increases luminal Gram-negative flora.…”

Clinical Implementation of Metabolomics

“…It is well known that in liver and skeletal muscles, tumor-induced negative nitrogen balance can promote intracellular production and extracellular release of glutamine (Medina et al, 1992). I n a d d i t i o n , i t w a s r e p o r t e d t h a t i n a c h ronic inflammatory process, the amino-acid metabolism could be influenced even in many remote organs: For instance, absorption of blood cysteine and methionine were both elevated immediately after glutathione synthesis was increased in the liver (Mercier et al, 2002).…”