Sustained Modifications of Protein Metabolism in Various Tissues in a Rat Model of Long-Lasting Sepsis

Abstract

1. Sepsis was induced in rats by an intravenous injection of live bacteria. Infected and pair-fed animals were studied before the infection, in an acute septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a late septic phase (day 10). Protein synthesis rates were measured in vivo after administration of a flooding dose of L[1-13C]valine. 2. During the acute phase, muscle protein loss associated with infection resulted from both a decrease in protein synthesis and an increase in proteolysis. During the chronic phase and the late phase, the increase of proteolysis in infected rats as compared with pair-fed animals persisted, worsening muscle atrophy. Skin protein synthesis rates were not significantly modified by infection. However, skin protein content decreased 6 and 10 days after infection, suggesting an increased proteolysis in response to sepsis. 3. Protein synthesis in liver of infected rats was twice that of pair-fed animals. Liver protein synthesis remained elevated in infected rats compared with pair-fed animals until day 10. Hypoalbuminaemia and high plasma concentrations of fibrinogen were evident at all periods studied. alpha 2-Macroglobulin and alpha 1-acid glycoprotein reached peak concentrations during the acute phase (concentrations increased 50 times in infected rats). On day 10, the levels of these proteins were still about 12-fold higher. 4. Protein synthesis rates were significantly increased in the digestive tract and lung of infected rats compared with pair-fed groups on days 2 and 6, but were similar in the two groups on day 10 post-infection. The fractional protein synthesis rate was increased 3-fold over the entire experimental period in the spleen. 5. The results show that sepsis stimulates protein synthesis in various tissues over a long time, and that skin, like muscle, can provide amino acids to the rest of the body.

Methionine metabolism in an animal model of sepsis

“…Sepsis markedly alters metabolism, in particular amino acid and protein metabolism (3,4). During transmethylation of methionine to homocysteine, methionine is transferred to S-adenosylmethionine (SAM; Figure 1).…”

Nutrition and pathology of weaner pigs: Nutritional strategies to support barrier function in the gastrointestinal tract

“…For example,7 showed decreased daily gain (11%), feed intake (29%), body protein accretion (38%) 191 and increased FCR (20%) compared with pigs with low immune system activation, 192 between 6 and 27 kg body weight. Moreover, Breuille et al (1994;1998) although the gastric pH is increased immediately after feeding and decreases with 227 time. However, the acid producing ability of newly-weaned piglets is not complete 228 (Cranwell, 1995) and pH of the piglet stomach is highly variable between 2.2 to 4.2 229 (Wellock et al, 2008a), which increase pathogen survival and transit to the small 230 intestine, as acidification of diet (Overland et al, 2008) pigs were euthanized on -1, 3 and 7 day post-infection.…”

Amino acid requirements in inflammatory states

“…Despite a major reduction in muscle protein synthesis after injury, a significant increase of whole body protein synthesis occurs, due to the anabolic response observed in numerous organs and tissues (Klasing and Austic 1984a;Breuillé et al 1998). To appreciate the impact of these anabolic responses, it is important first to identify the main organs involved and, second, to know the synthesis rate and the composition of the proteins involved.…”

“…Protein synthesis was measured 2 d after infection. Data adapted from Breuillé et al (1994Breuillé et al ( , 1998. For personal use only.…”

“…In critically ill patients, up to 20% of body protein is lost in 3 wk, mainly from skeletal muscle (Plank and Hill 2000). The net catabolism of muscle proteins is the result of both decreased protein synthesis and sustained increased protein breakdown and produces an increased flow of amino acids from muscle to visceral organs (Klasing and Austic 1984a,b;Voisin et al 1996;Breuillé et al 1998;Jahoor et al 1999). These amino acids are used for energy supply and for processes activated as part of the body defense mechanisms.…”