Whole body leucine and lysine metabolism studied with [1-13C]leucine and [α-15N]lysine: Response in healthy young men given excess energy intake

An excess intake of dietary energy in adult subjects enhances body N balance but the mechanism(s) responsible remains unknown. Thus, dynamic aspects of metabolism of whole body leucine and lysine were explored in healthy young adult men, receiving adequate or excess energy intakes, using a primed, continuous intravenous infusion of a mixture of L-¹³C]leucine and L-α-¹⁵N]lysine to provide a constant enrichment of plasma free leucine and lysine over a period of 2 hr. Twelve subjects were studied with the labeled amino acids following an overnight fast (post-absorptive state) and 12 additional subjects while consuming small isocaloric, isonitrogenous horly meals (fed state). Preceding each infusion, subjects were adapted for 7 days to experimental diets, providing a constant and barely adequate protein intake of 0.6 g/kg body weight/day, at either a maintenance energy intake, determining from estimates of usual food intake that maintain body weight, or an energy intake 25% greater than the maintenance level. The excess non-protein energy intake was given as an isocaloric mixture of carbohydrate and fat (eight subjects) or entirely as either carbohydrate or fat (eight subjects each). Whole body leucine and lysine flux remained unchanged with excess energy intakes, regardless of the source of energy substrate. Based on the combined data with all energy intake sources, the rate of leucine oxidation was significantly reduced and the rate of leucine incorporation into body protein showed a small increase with excess energy intakes. Thus, when expressed as net protein gain (leucine incorporation into body protein minus leucine release from protein breakdown) a significantly greater rate of body protein retention occurred with excess energy intake and this was more marked for the high carbohydrate diets. Mean change in body leucine retention determined by ¹³C-leucine was in good agreement with that calculated from alterations in overall N balance. In addition, the rate of inflow of leucine and of lysine into the metabolic pool via tissue protein breakdown was reduced with ingestion of meals. These results indicate that excess energy intake improves overall body N balance by reducing amino acid oxidation and enhancing protein synthesis. Furthermore, these effects are particularly evident at a time when passage of amino acids to tissues is stimulated by ingestion and absorption of meals.