Plasma LEAP2 concentration is associated with energy intake and postprandial insulin increase depending on meal size but not weight status in men

Aims: While LEAP2 is increasingly recognized as an appetite-regulating hormone, its role in meal regulation and the dynamics of postprandial LEAP2 concentrations remain poorly understood in humans. The aim of the study was to (1) assess postprandial LEAP2 concentrations following a recommended-energy breakfast, exploring potential association with voluntary energy intake and modulation by weight status and (2) to examine the interplay between postprandial LEAP2 and insulin concentrations. Materials and methods: Eighty-four men with normal weight (NW) and 48 with overweight or obesity (OW/OB) received a test meal; pre- and postprandial LEAP2 and insulin concentrations were assessed. Energy intake was calculated by multiplying the weight of the food items consumed by their energy content according to their label. Results: Fasting LEAP2 was positively associated with glycaemia in participants with NW [Beta (95% CI): 0.289 (0.058, 0.520), p = 0.015] but not with OW/OB. Sixty-seven participants consumed the entire test meal (CMC, complete meal consumption); the rest consumed only part (PMC, partial meal consumption). Postprandial LEAP2 concentration was higher in the PMC (p = 0.017) than in the CMC group and in participants with OW/OB (p = 0.046). Pre (p = 0.027) and postprandial (p = 0.031) LEAP2 was inversely related to ingested calories, but only in PMC and independent of weight status. Postprandial insulin increase (p < 0.001) depended on LEAP2 only in CMC (p = 0.017) and was independent of weight status. Conclusions: The relationship of LEAP2 with energy intake and postprandial insulin increase is influenced by meal size but not weight status. Keywords: LEAP2; energy intake; insulin; meal size.