Hypermetabolism and Protein Catabolism

The progression of disease in HIV patients is associated with an increased REE [60]; however, weight loss is better correlated with calorie intake than with REE [73]. While opportunistic infections, malignancies, and high levels of cytokines and hormones in tissues may explain hypermetabo lism, it is not clear whether increased REE alone (Fig. 5) can cause wasting, in the absence of other processes [74,75].

Depending on the type of cachexia, the body's protein compartment undergoes several modifications, which are, in some cases, not related to fat changes [22]. New insights regarding muscle atrophy occurring in aging, AIDS, diabetes, immobility, and space flight have been gained in the last few years. For example, it is now known that ubiquitin ligases are involved in the breakdown of muscle proteins [76]. An acute calorie defect, e.g. a total 24-h fast, forces the organism to use energy reserves, so that approximately 150 g of fat and 60 g of protein are burned. Subsequently, energy-saving mechanisms become involved. These reduce protein breakdown by as much as threefold, whereas the energy withdrawal from adipose tissue remains unchanged [34]. Basal metabolism accounts for about a fifth of the calories normally consumed at rest. In contrast, serious infection induces acute protein loss (which may be > 120 g/day) [32]. During the septic period, starvation

Fig. 5. Resting energy expenditure (REE) and caloric intake in HIV infection. REE increases according to disease progression, while caloric intake becomes insufficient to maintain basal needs. OI, opportunistic infection

does not activate the energy-saving mechanism that occurs in the absence of infection, so that calorie withdrawal causes a further protein loss that can reach 90 g/day [32,34]. In sepsis, the basal energy requirement increases because of the hyperthermia [77] induced by cytokines and futile cycles [78].

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