Contributions of upper gut hormones and motility to the energy intake-suppressant effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis

Abstract

We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed‐effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within‐subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon‐like peptide‐1 (GLP‐1) and time‐to‐peak GLP‐1 concentrations, GLP‐1 AUC and bloating scores (P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake (P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative contributions from a range of interrelated factors.

Effects of Intraduodenal Infusion of the Bitter Tastant, Quinine, on Antropyloroduodenal Motility, Plasma Cholecystokinin, and Energy Intake in Healthy Men

“…In line with the lack of effect of Q-HCl to modulate upper GI motility, particularly pyloric pressures, or stimulate CCK, both of which we have identified as key determinants of the subsequent suppression of energy intake in response to duodenal nutrients, 1,34 we found no effect of Q-HCl to reduce appetite or energy intake. In a recent study, DB reduced hunger ratings in the fasting state, and decreased hunger and increased satiety after a meal, but did not significantly reduce caloric intake from a standardized meal, with substantial variability between individuals.…”

Intraduodenal Administration of L-Valine Has No Effect on Antropyloroduodenal Pressures, Plasma Cholecystokinin Concentrations or Energy Intake in Healthy, Lean Men

“…Based on these findings, we hypothesised that intraduodenal infusion of L-valine would also reduce energy intake. In contrast to our expectation, L-valine was ineffective—it did not affect subsequent energy intake, nor GI functions of relevance to the regulation of energy intake, specifically the stimulation of plasma CCK and pyloric pressures [32,33]. While it is possible that L-valine may be an amino acid that does not play a role in appetite regulation, it is worth noting the important contributory roles of orosensory and gastric influences (which we bypassed in the current study) with gut hormone release and the modulation of energy intake [34,35].…”

Gastrointestinal Sensing of Meal-Related Signals in Humans, and Dysregulations in Eating-Related Disorders

“…This is achieved by well-characterised effects of nutrients on pressures in the antropyloroduodenal region [27], mediated by gut hormones released in response to nutrients [2,3,10]. Nutrients in the intestinal lumen, particularly lipid and protein, also modulate appetite and subsequent energy intake [28,29], and changes in both motility and gut hormones play critical roles [30,31].…”

“…These effects occur in a load-dependent manner, and are associated with the suppression of energy intake [28,32]. In fact, the magnitude of the stimulation of pyloric pressures and plasma CCK, as indicators of the GI sensing of nutrients, have been identified as independent determinants of energy intake in response to intraduodenal administration of particularly fat and also protein [30,31].…”