Effects of intragastric administration of L-tryptophan on appetite and gut hormone release in healthy, normal weight and obese subjects.

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Obesity has reached epidemic proportions globally and is associated with serious co-morbidities, including type 2 diabetes. Once adipose tissue has been accumulated, and food intake is limited by low calorie diets, counter-regulatory mechanisms induce an increase in appetite and a decrease in energy expenditure, which makes weight loss very difficult to maintain. To combat the global burden of obesity and its co-morbidities, a major challenge lies in the development of effective therapies that increase fullness and satiety, and result in improvements in blood glucose control, while lacking adverse effects that are often associated with current therapies. There is increasing evidence that nutrient stimuli in the gastrointestinal tract play a central role in the control of energy intake and blood glucose. Proteins, and their building blocks, amino acids, are of interest, as high-protein diets are very effective for weight loss, particularly loss of fat, rather than muscle mass, and for improving postprandial glycaemic control, in obese individuals with and without type 2 diabetes. There is some evidence that a number of amino acids (including L-tryptophan) also have effects on energy intake, blood glucose and gut function in humans. We have previously investigated the effects of intraduodenal tryptophan and found that its effects to reduce subsequent energy intake were related to plasma cholecystokinin and tryptophan concentrations prior to the test meal. Thus, amino acids, here specifically tryptophan, may represent potential therapeutic approaches for obesity and type 2 diabetes. We have recently evaluated the effects of intragastric tryptophan at 3 g on gastric emptying, blood glucose, gut hormones, and appetite following a mixed-nutrient drink. Energy intake at a subsequent buffet style meal was also assessed. L-tryptophan slowed gastric emptying in both lean and obese groups. While overall energy intake was not affected, there was a decrease in energy intake in approximately half the subjects of each group, but less so in the obese. In the lean group, energy intake was found to be related to elevated concentrations of plasma tryptophan. A limitation of this study design may have been too long a duration between tryptophan administration and the meal at which energy intake was assessed (1 hr 15 min), thus mitigating the overall effect on energy intake. This new study has been designed with a shorter duration between tryptophan administration and buffet meal (30 min) and will investigate the effects of intragastric administration of L-tryptophan, vs saline control, on energy intake at a subsequent ad libitum buffet style meal, and the relationship with plasma gut hormone and tryptophan concentrations, appetite perceptions and intragastric volume in healthy, normal weight and obese, subjects.

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