Increased plasma Gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting

Muscle protein wasting occurs in human immunodeficiency virus (HIV)-infected individuals and is often the initial indication of acquired immunodeficiency syndrome (AIDS). Little is known about the alterations in muscle protein metabolism that occur with HIV infection. Nine subjects with AIDS wasting (CD4 < 200/mm(3)), chronic stable opportunistic infections (OI), and greater than or equal to 10% weight loss, fourteen HIV-infected men and one woman (CD4 > 200/mm(3)) without wasting or OI (asymptomatic), and six HIV-seronegative lean men (control) received a constant intravenous infusion of [1-C-13]leucine (Leu) and [2-N-15]glutamine (Gln). Plasma Leu and Gln rate of appearance (R-a), whole body Leu turnover, disposal and oxidation rates, and [C-13]Leu incorporation rate into mixed muscle protein were assessed. Total body muscle mass/fat-free mass was greater in controls (53%) than in AIDS wasting (43%; P = 0.04). Fasting whole body proteolysis and synthesis rates were increased above control in the HIV+ asymptomatic group and in the AIDS-wasting group (P = 0.009). Whole body Leu oxidation rate was greater in the HIV+ asymptomatic group than in the control and AIDS-wasting groups (P < 0.05). Fasting mixed muscle protein synthesis rate was increased in the asymptomatic subjects (0.048%/h; P = 0.01) but was similar in AIDS-wasting and control subjects (0.035 vs. 0.037%/h). Plasma Gin R-a, was increased in AIDS-wasting subjects but was similar in control and HIV+ asymptomatic subjects (P < 0.001). These findings suggest that AIDS wasting results from 1) a preferential reduction in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle protein synthesis while whole body protein synthesis is increased, and 3) a significant increase in Gin release into the circulation, probably from muscle. Several interesting explanations for the increased Gin R-a, in AIDS wasting exist.