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1 Divisions of Metabolism, Endocrinology and Diabetes, and Infectious Disease, Washington University School of Medicine, St. Louis, Missouri 63110; and 2 Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808-4124
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/mm3), chronic stable
opportunistic infections (OI), and 
10% weight loss, fourteen
HIV-infected men and one woman (CD4 > 200/mm3) without wasting or OI
(asymptomatic), and six HIV-seronegative lean men (control) received a
constant intravenous infusion of [1-13C]leucine (Leu)
and [2-15N]glutamine
(Gln). Plasma Leu and Gln rate of appearance
(Ra), whole body Leu turnover,
disposal and oxidation rates, and
[13C]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 Gln Ra 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 Gln
release into the circulation, probably from muscle. Several interesting
explanations for the increased Gln
Ra in AIDS wasting exist.
acquired immunodeficiency syndrome-wasting syndrome; immune cell function; amino acid metabolism; metabolic complications; stable isotopes; mass spectrometry; leucine; glutamine
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