Dietary protein reduces energy intake in following meals by signaling directly or indirectly to the brain. We recently observed differences in plasma amino acid kinetics and intra-gastric behavior between micellar casein (MC) and sodium caseinate (SC) in pigs, two factors that impact food intake. Our objective was to clarify whether the supramolecular structure of casein, given as a preload to pigs, impacts on subsequent food intake. Overnight fasted pigs were allowed to consume casein drinks differing in casein macromolecular structure (SC vs MC) within 5 min in a cross-over study. Ad libitum intake of their regular feed was assessed during 1 h, either 1 or 4 h after casein drink ingestion. To evaluate the potential mechanisms at play, gastric emptying of the casein drinks radiolabeled with 99 Tc-colloïd was followed using gamma-scintigraphy while plasma kinetics of ghrelin, GLP-1, insulin and free amino acids were evaluated. The amount of feed consumed 1, but not 4 h, after SC ingestion was lower than the amount of feed consumed after MC ingestion (P = 0.03). Gastric emptying parameters, plasma ghrelin, GLP-1 and insulin kinetics after both types of casein ingestion were not significantly different (P > 0.05). However, plasma free amino acid concentrations, known to reduce food intake, increased after both SC and MC ingestion but was greater after SC than MC ingestion from 60 to 120 min (P = 0.009). In conclusion, casein supramolecular structure in a preload drink impacts differently subsequent energy intake, likely due to difference in amino acid bioavailability. Micellar casein exhibits less anorectic effect than sodium caseinate, a property that could benefit population with high protein need but low appetite such as elderly., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MH and AB are employees of Ingredia SA. SG, GH, LLN, AC, DD, GB have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)