The Journal of Nutrition Methodology and Mathematical Modeling The Dynamics of Gastric Emptying and Self-Reported Feelings of Satiation Are Better Predictors Than Gastrointestinal Hormones of the Effects of Lipid Emulsion Structure on Fat Digestion in Healthy Adults—A Bayesian Inference Approach 1–3 Andreas Steingoetter, 4,5,9 * Simon Buetikofer, 4,9 Jelena Curcic, 4,5 Dieter Menne, 6 Jens F Rehfeld, 7 Michael Fried, 4 Werner Schwizer, 4 and Tim J Wooster 8 4 Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland; 5 Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland; 6 Menne Biomed Consulting, Tu ¨ bingen, Germany; 7 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, København, Denmark; and 8 Nestl´ e Research Center, Lausanne, Switzerland Abstract Background: Limited information exists on the relation between fat emulsion structure and its effect on the release of gastrointestinal hormones and feelings of satiation. Objective: We investigated the impact of fat emulsion droplet size, gravitational and acid stability, and redispersibility on gastrointestinal responses and sought to deduce the relative importance of the hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and peptide YY (PYY) in controlling fat emptying and related satiation. Methods: Within a randomized, double-blind, 4-armed crossover study, an extensive data set was generated by MRI of gastric function, analysis of hormone proﬁles, and ratings of satiation in healthy participants [10 women and 7 men with a mean 6 SD age of 25 6 7 y and body mass index (in kg/m 2 ) of 22 6 1] after intake of 4 different fat emulsions. Iterative Bayesian model averaging variable selection was used to investigate the inﬂuence of hormone proﬁles in controlling fat emulsion emptying and satiation. Results: The emulsion structure had a distinct effect on the gastric emptying (primary outcome), gastrointestinal hormone proﬁles, and ratings of satiation (secondary outcomes). Gravitational and acid stability were stronger modulators of fat emptying and hormone proﬁles than were emulsion droplet size or redispersibility. Cholecystokinin and PYY were most strongly affected by fat emulsion instability and droplet size. Although both hormones were relevant predictors of gastric emptying, only PYY was identiﬁed as a relevant predictor of satiation. Conclusions: This work indicates that evenly dispersed, stable, small-emulsion droplets within the stomach lead to prolonged gastric distension, longer ghrelin suppression, and accelerated fat sensing (cholecystokinin and PPY), triggering prolonged feelings of satiation. It suggests that the effects of emulsion instability and droplet size on energy consumption are best studied by assessing changes in gastric emptying and ratings of satiation rather than changes in venous hormone proﬁles. This trial was registered at clinicaltrials.gov as NCT01253005. J Nutr 2017;147:706–14. Keywords: acid stability, cholecystokinin, droplet size, fat emulsion, gastric emptying, ghrelin, glucagon-like peptide 1, MRI, peptide YY, satiation Introduction Fat digestion is important for achieving balanced nutrition (1, 2). However, fat is calorie-dense and seemingly low in satiation value, especially when regularly consumed over long periods of time (3, 4). Hence, with regard to the current obesity epidemic, it is important to understand the relation between fat digestion and its inﬂuence on feelings of fullness and hunger (4–6). Relevant parameters of fat digestion that affect satiation are the rate of gastric emptying and speed of lipolysis in the stomach and proximal small bowel (7, 8). A current hypothesis is that intraduodenal fat digesta act as a short-term control on food intake via neurohormonal-mediated negative-feedback path- ways that delay gastric emptying and lead to prolonged gastric distension, which in turn prolongs ghrelin suppression, resulting ã 2017 American Society for Nutrition. 706 Manuscript received July 11, 2016. Initial review completed August 10, 2016. Revision accepted January 25, 2017. First published online February 22, 2017; doi:10.3945/jn.116.237800. Downloaded from https://academic.oup.com/jn/article-abstract/147/4/706/4669666 by guest on 06 June 2020