Flux of amino acids and energy substrates across the leg in weight-stable HIV-infected patients with acute opportunistic infections: indication of a slow protein wasting process

Abstract

Increased whole-body proteolysis with muscle protein net degradation has been suggested as one of the causes of weight loss in patients infected with human immunodeficiency virus (HIV). We studied the exchange rates of amino acids and energy substrates across the lower extremity in 16 HIV patients and 16 age-matched controls with similar body cell mass. The patients had either opportunistic infections or chronic diarrhea but no signs of clinical malnutrition. The following findings were obtained in the HIV patients: an augmented peripheral net release of arginine and lysine; an increase in both the negative arterial-venous difference and the efflux of the nitrogen contained in nonmetabolized amino acids; diminished export of 3-methylhistidine; lowered plasma and erythrocyte amino acid concentrations; reduced output of glycerol and furthermore; and neither a net release nor a net uptake of free fatty acids. The findings concerning nitrogen metabolism support the hypothesis that, in the presence of a reduction in protein breakdown, peripheral protein synthesis is severely depressed, making a slow protein wasting process likely to occur. The balances of glycerol and free fatty acids are due not only to the leg tissues but perhaps also in part to increased net retention of these substrates by skeletal muscle.

Effects of tuberculosis and HIV infection on whole-body protein metabolism during feeding, measured by the [15N]glycine method

“…Initial reports in which [ 13 C]leucine was used to assess changes in protein metabolism suggest that both protein synthesis and degradation increased (20). Later studies indicated that, in wasted patients, muscle protein synthesis might be downregulated, even when there is an overall increase in whole-body synthesis (21,22) and that the extent of change might be responsive to the level of activity or to nutritional or hormonal modulation (12,23,24). In addition to differences in body composition and nutritional intake, the contrasting results between studies may also reflect the marked clinical heterogeneity of patients with HIV disease.…”

Moderate-Intensity Exercise Improves Body Composition and Improves Physiological Markers of Stress in HIV-Infected Men

“…Cortisol, which is elevated in HIV-infected persons [15–17], is a potent catabolic hormone, which increases rates of protein degradation and slows protein synthesis rates, especially in skeletal muscle [18]. Serum cortisol levels also appear to be the best predictor for insulin resistance followed by interleukin-6 (IL-6) in persons with inflammatory conditions [19].…”

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study

“…Likewise, it has been documented that people infected with HIV experience changes at multiple levels of the hypothalamic-pituitary-adrenal axis, which can cause elevated cortisol levels ( 33 ). This alteration, being a potent catabolic pathway, could also increase protein degradation rates and slow down protein synthesis rates, especially in muscle mass; this is why it is implicated in muscle wasting associated with HIV infection ( 34 ).…”