An endocrine and metabolic definition of the intermeal interval in humans: evidence for a role of leptin on the prandial pattern through fatty acid disposal

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Abstract
Background: It has been proposed that leptin provides a hormonal link between adipose stores and food intake. Objective: This study investigated the role of leptin in the prandial pattern. Design: In experiment 1, a spontaneous prandial pattern was recreated in 6 young, normal-weight men who were deprived of time cues and had blood withdrawn continuously at a frequency of one tube every 5 min. Meals were consumed ad libitum and dinner was requested voluntarily. Data from a second experiment, conducted in 8 subjects, were used to confirm the changes in leptin during the intermeal interval (IMI). Results: Plasma leptin gradually rose to a peak (62 ± 18% of the lunch concentration) during the IMI and declined before the dinner request (−21 ± 4% of the peak concentration). This preprandial decline was confirmed in experiment 2 (−15 ± 9%). The leptin concentration at lunch and fat-free mass were the only significant predictors of the IMI (both: r2 = 0.91, P = 0.03). With fat intake at lunch, the leptin concentration at lunch was a positive predictor of the area under the curve of plasma fatty acids during the IMI (r2 = 0.95, P = 0.01). Moreover, the leptin concentration at lunch was negatively correlated with energy intake in the first course of this meal (r = −0.95, P < 0.005). A similar result was found at dinner (r = −0.85, P < 0.05). Last, the change in leptin was predicted accurately by changes in glucose, triacylglycerol, and fatty acids (r2 = 0.87, P < 10–5). Conclusion: Plasma leptin concentrations increase during a spontaneous IMI and decline before the onset of a meal. The results argue for a role of leptin in the prandial pattern through fatty acid peripheral disposal.