Many of the features of BCAA metabolism in the tumor-bearing state are similar to the other disease states that feature involuntary weight loss and skeletal muscle atrophy. These states are generally characterized by altered BCAA availability (low BCAA intakes, elevated rates of BCAA oxidation, and gluconeogenesis), which are concurrent with activation of proteolysis and suppression of protein synthesis in skeletal muscle and ultimately lead to erosion of lean tissue mass. These features in turn imply BCAA deficiency compared with whole-body requirements and are the basis of suggestions for dietary supplementation with BCAA or their metabolites. Recent studies on BCAA supplementation in cancer focus on leucine and its derivative, beta-methyl beta-hydroxybutyrate, as regulators of skeletal muscle metabolism, although their relative efficacy is unknown. However, what would otherwise be a relatively straightforward consideration of amino acid supply and demand is confounded by the presence of the tumor and its potential utilization of BCAA for its proliferative and invasive activities. Positron emission tomography with (11)C-leucine, used for in vivo tumor imaging, points to the high avidity of tumor amino acid uptake. These features have incited research in opposing directions, probing BCAA deprivation, with a view to limiting tumor growth, as well as BCAA supplementation, with a view to supporting maintenance of host lean tissue. No clear conclusion is presently available from the sum of these efforts. Animal models with relevant clinical features are essential to determine if amino acid therapy can alter the balance between the host and the tumor in a manner that favors the host overall.

Prader-Willi syndrome (PWS) is a rare genetic disorder associated with excessive weight gain. Hyperphagia associated with PWS may result in higher energy intake, but alterations in energy expenditure may also contribute to energy imbalance. The purpose of this critical literature review is to determine the presence of alterations in energy expenditure in individuals with PWS. Ten studies that measured total energy expenditure (TEE), resting energy expenditure (REE), sleep energy expenditure (SEE), activity energy expenditure (AEE), and diet induced thermogenesis (DIT) were included in this review. The studies provided evidence that absolute TEE, REE, SEE, and AEE are lower in individuals with PWS than in age-, sex-, and body mass index-matched individuals without the syndrome. Alterations in lean body mass and lower physical activity amounts appear to be responsible for the lower energy expenditure in PWS rather than metabolic differences. Regardless of the underlying mechanism for lower TEE, the estimation of energy requirements with the use of equations derived for the general population would result in weight gain in individuals with PWS. The determination of energy requirements for weight management in individuals with PWS requires a more comprehensive understanding of energy metabolism. Future studies should aim to comprehensively profile all specific components of energy expenditure in individuals with PWS with the use of appropriately matched controls and gold standard methods to measure energy metabolism and body composition. One component of energy expenditure that is yet to be explored in detail in PWS is DIT. A reduced DIT (despite differences in fat free mass), secondary to hormonal dysregulation, may be present in PWS individuals, leading to a reduced overall energy expenditure. Further research exploring DIT in PWS needs to be conducted. Dietary energy recommendations for weight management in PWS have not yet been clearly established.

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Our aim was to examine the effect of acute inflammation localized in the colon and early macronutrient restriction on protein synthesis in a piglet model. In a 2 x 2 factorial design, piglets (n = 32) were fed an adequate or macronutrient-restricted diet with or without dextran sulfate-induced colitis for 7 d. The stable isotope tracer L-[5,5,5-(2)H(3)]leucine was infused to determine protein kinetics at the whole-body level and synthesis of tissue and plasma proteins. In the well-nourished state, colitis did not affect weight gain or protein kinetics except for an increase in albumin synthesis (P < 0.05). Macronutrient restriction alone caused a general slowing of protein metabolism including decreased weight gain (P < 0.0004), whole-body protein turnover (P < 0.0001), and liver (P < 0.01) and plasma protein (P < 0.03) synthesis. However, in the presence of macronutrient restriction, colitis compromised weight gain further (P < 0.02) and decreased muscle protein synthesis (P < 0.05) due to a redistribution of protein metabolism that supported enhanced synthesis of plasma proteins. The increased contribution of plasma protein synthesis to whole-body protein turnover was attributable mainly to increased synthesis of albumin (P < 0.006). Concentrations of plasma proteins were unaffected despite dramatic changes in their synthesis rates, thereby underestimating the effects of malnutrition and colitis on protein metabolism. Increased synthesis of plasma proteins, particularly the negative acute phase reactant albumin, compromises weight gain and muscle protein synthesis only when macronutrient intake is inadequate, underscoring the role of adequate nutrition in preventing growth impairment and muscle wasting in acute inflammation. These results suggest that the hypoalbuminemia of inflammatory bowel disease should not be attributed to decreased synthesis.

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