Tumor necrosis factor α attenuates glutamine-enhanced skeletal muscle protein synthesis in rats

Abstract 

Glutamine has been widely used in critical illness, surgery, and injury. Previous studies showed that the use of glutamine in nutritional regimens for patients with sepsis was not as effective as in patients of trauma, especially in the early stage of sepsis. The objective of this study was to determine whether the regulation of glutamine on protein synthesis in skeletal muscle could be inhibited by tumor necrosis factor α (TNF-α), one of the major mediators in sepsis in a rat model. Thirty male Sprague-Dawley rats were randomly assigned into 3 groups: total parenteral nutrition (TPN; control), Gln (treated with glutamine), and TNF-α (treated with glutamine and TNF-α). All rats received isonitrogenous and isoenergetic TPN solutions for 3 days. The control group was supplemented with TPN, the glutamine group was given glutamine-enriched TPN, and the TNF-α group was supplemented with glutamine-enriched TPN followed by intravenously infused TNF-α in the last 24 hours. In the last 30 minutes, all rats were mainlined with [l-¹⁵N]leucine. The concentrations of TNF-α and glutamine in plasma and skeletal muscle were measured, and the fractional synthesis rate was assessed. The level of TNF-α in the TNF-α group was the highest among the 3 groups. The glutamine concentration was elevated more in the TNF-α group than in the other 2 groups (P < .05). The fractional synthesis rate increased significantly in the TNF-α and Gln groups than that in the control group, and it was the highest in the Gln group (P < .05). In conclusion, TNF-α could attenuate protein synthesis in the skeletal muscle stimulated by glutamine in the early stage of sepsis in rats.

Keywords: Total parenteral nutrition, Glutamine, TNF-α, Stable isotope, Fractional synthesis rate, Rat