The incidence of obesity is increasing rapidly. Research efforts for effective treatment strategies still focus on diet and exercise programmes, the individual components of which have been investigated in intervention trials in order to determine the most effective recommendations for sustained changes in bodyweight. The foremost objective of a weight-loss trial has to be the reduction in body fat leading to a decrease in risk factors for metabolic syndrome. However, a concomitant decline in lean tissue can frequently be observed. Given that fat-free mass (FFM) represents a key determinant of the magnitude of resting metabolic rate (RMR), it follows that a decrease in lean tissue could hinder the progress of weight loss. Therefore, with respect to long-term effectiveness of weight-loss programmes, the loss of fat mass while maintaining FFM and RMR seems desirable. Diet intervention studies suggest spontaneous losses in bodyweight following low-fat diets, and current data on a reduction of the carbohydrate-to-protein ratio of the diet show promising outcomes. Exercise training is associated with an increase in energy expenditure, thus promoting changes in body composition and bodyweight while keeping dietary intake constant. The advantages of strength training may have greater implications than initially proposed with respect to decreasing percentage body fat and sustaining FFM. Research to date suggests that the addition of exercise programmes to dietary restriction can promote more favourable changes in body composition than diet or physical activity on its own. Moreover, recent research indicates that the macronutrient content of the energy-restricted diet may influence body compositional alterations following exercise regimens. Protein emerges as an important factor for the maintenance of or increase in FFM induced by exercise training. Changes in RMR can only partly be accounted for by alterations in respiring tissues, and other yet-undefined mechanisms have to be explored. These outcomes provide the scientific rationale to justify further randomised intervention trials on the synergies between diet and exercise approaches to yield favourable modifications in body composition.

High-intensity exercise leads to reductions in muscle substrates (ATP, PCr6, and glycogen) and a subsequent accumulation of metabolites (ADP, P, H(+), and Mg(+)) with a possible increase in free radical production. These factors independently and collectively have deleterious effects on muscle, with significant repercussions on high-intensity performance or training sessions. The effect of carnosine on overcoming muscle fatigue appears to be related to its ability to buffer the increased H(+) concentration following high-intensity work. Carnosine, however, has other roles such as an antioxidant, a metal chelator, a Ca(2+) and enzyme regulator, an inhibitor of protein glycosylation and protein-protein cross-linking. To date7comma; only 1 study has investigated the effects of carnosine supplementation (not in pure form) on exercise performance in human subjects and found no improvement in repetitive high-intensity work. Much data has come from in vitro work on animal skeletal muscle fibers or other components of muscle contractile mechanisms. Thus further research needs to be carried out on humans to provide additional understanding on the effects of carnosine in vivo.

Obesity-related metabolic disorders are characterized by mild chronic inflammation, leukocyte infiltration, and tissue fibrosis as a result of adipocytokine production from the expanding white adipose tissue. Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates systemic anti-inflammatory processes and, therefore, may be altered with increasing adiposity in humans. Paradoxically, we found that plasma AnxA1 concentrations inversely correlated with BMI, total percentage body fat, and waist-to-hip ratio in human subjects. Plasma AnxA1 was also inversely correlated with plasma concentrations of the acute-phase protein, C-reactive protein (CRP), and the adipocytokine leptin, suggesting that as systemic inflammation increases, anti-inflammatory AnxA1 is reduced. In addition, AnxA1 gene expression and protein were significantly up-regulated during adipogenesis in a human adipocyte cell line compared to vehicle alone, demonstrating for the first time that AnxA1 is expressed and excreted from human adipocytes. These data demonstrate a failure in the endogenous anti-inflammatory system to respond to increasing systemic inflammation resulting from expanding adipose tissue, a condition strongly linked to the development of type 2 diabetes and cardiovascular disease. These data raise the possibility that a reduction in plasma AnxA1 may contribute to the chronic inflammatory phenotype observed in human obesity.

Objectives: To assess the changes in measures of fatigue after meals of varying composition, and to compare the relation of the fatigue with changes in the plasma tryptophan:large neutral amino acids (Trp:LNAA) ratio. Subjects: Sixteen healthy volunteers were recruited from staff and students at the College. Design: Subjects were tested for central and peripheral fatigue using a visual analogue scale,¯icker fusion frequency, grip strength, reaction time and wrist ergometry. In addition, plasma amino acid concentrations and Trp:LNAA ratio were determined. Measurements were made before, and at 1, 2, 3 and 4 h after drinking one of three liquid test meals. The meals were isoenergetic (1672 kJ) and were of mixed carbohydrate, fat and protein, or of pure carbohydrate or pure fat. Setting: Department of Human Nutrition. Results: Subjects consuming the pure carbohydrate meal reported more subjective feelings of fatigue and had slower reaction times. Aspects of central fatigue were greater in subjects consuming a pure fat meal. The Trp:LNAA ratio was depressed in those consuming a pure fat or mixed meal and raised only after pure carbohydrate. Conclusions: Central and subjective fatigue may be in¯uenced by raised plasma free tryptophan to competitor amino acid ratios induced by carbohydrate intake but other aspects of central arousal are affected by fat intake.