Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects

The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.Deirdre O’Donovan, Christine Feinle-Bisset, Judith Wishart and Michael Horowit

Upper gastrointestinal sensitivity to meal-related signals in adult humans - relevance to appetite regulation and gut symptoms in health, obesity and functional dyspepsia

Available online 21 March 2016Both the stomach and small intestine play important roles in sensing the arrival of a meal, and its physico-chemical characteristics, in the gastrointestinal lumen. The presence of a meal in the stomach provides a distension stimulus, and, as the meal empties into the small intestine, nutrients interact with small intestinal receptors, initiating the release of gut hormones, associated with feedback regulation of gastrointestinal functions, including gut motility, and signaling to the central nervous system, modulating eating behaviours, including energy intake. Lipid appears to have particularly potent effects, also in close interaction with, and modulating the effects of, gastric distension, and involving the action of gut hormones, particularly cholecystokinin (CCK). These findings have not only provided important, and novel, insights into how gastrointestinal signals interact to modulate subjective appetite perceptions, incl. Fullness, but also laid the foundation for an increasing appreciation of the role of altered gastrointestinal sensitivities, e.g. as a consequence of excess dietary intake in obesity, or underlying the induction of gastrointestinal symptoms in functional dyspepsia (a condition characterized by symptoms, including bloating, nausea and early fullness, amongst others, after meals, particularly those high in fat, in the absence of any structural or functional abnormalities in the gastrointestinal tract). This paper will review the effects of dietary nutrients, particularly lipid, on gastrointestinal function, and associated effects on appetite perceptions and energy intake, effects of interactions of gastrointestinal stimuli, as well as the role of altered gastrointestinal sensitivities (exaggerated, or reduced) in eating-related disorders, particularly obesity and functional dyspepsia.Christine Feinle-Bisse

Appetite and satiety control—contribution of gut mechanisms

The prevalence of obesity, and its comorbidities, particularly type 2 diabetes, cardiovascular and hepatic disease and certain cancers, continues to rise at an alarming rate worldwide [...].Christine Feinle-Bisset and Michael Horowit

A dish-based semi-quantitative food frequency questionnaire for assessment of dietary intakes in epidemiologic studies in Iran: design and development

BACKGROUND: Earlier forms of food frequency questionnaire (FFQ) used in Iran have extensive lists of foods, traditional categories and food-based design, mostly with the interviewer-administered approach. The aim of the current paper is to describe the development of a dish-based, machine-readable, semi-quantitative food frequency questionnaire (DFQ). METHODS: Within the framework of the Study on the Epidemiology of Psychological, Alimentary Health and Nutrition project, we created a novel FFQ using Harvard FFQ as a model. RESULTS: THE FOLLOWING STEPS WERE TAKEN TO DEVELOP THE QUESTIONNAIRE: Construction of a list of commonly consumed Iranian foods, definition of portion sizes, design of response options for consumption frequency of each food item and finally a pilot test of the preliminary DFQ. From a comprehensive list of foods and mixed dishes, we included those that were nutrient-rich, consumed reasonably often or contributed to between-person variations. We focused on mixed dishes, rather than their ingredients, along with foods. To shorten the list, the related food items or mixed dishes were categorized together in one food group. These exclusions resulted in a list of 106 foods or dishes in the questionnaire. The portion sizes used in the FFQ were obtained from our earlier studies that used dietary recalls and food records. The frequency response options for the food list varied from 6-9 choices from "never or less than once a month" to "12 or more times per day". CONCLUSIONS: The DFQ could be a reasonable dietary assessment tool for future epidemiological studies in the country. Validation studies are required to assess the validity and reliability of this newly developed questionnaire.AH Keshteli, Ahmad Esmaillzadeh, Somayeh Rajaie, Gholamreza Askari, Christine Feinle-Bisset and Peyman Adib

Effects of duodenal infusion of lauric acid and L-tryptophan, alone and combined, on fasting glucose, insulin and glucagon in healthy men

Published: 7 November 2019The fatty acid, lauric acid ('C12'), and the amino acid, tryptophan ('Trp'), when given intraduodenally at loads that individually do not affect energy intake, have recently been shown to stimulate plasma cholecystokinin, suppress ghrelin and reduce energy intake much more markedly when combined. Both fatty acids and amino acids stimulate insulin secretion by distinct mechanisms; fatty acids enhance glucose-stimulated insulin secretion, while amino acids may have a direct effect on pancreatic β cells. Therefore, it is possible that, by combining these nutrients, their effects to lower blood glucose may be enhanced. We have investigated the potential for the combination of C12 and Trp to have additive effects to reduce blood glucose. To address this question, plasma concentrations of glucose, insulin and glucagon were measured in 16 healthy, lean males during duodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12+Trp (0.4 kcal/min), for 90 min. Both C12 and C12+Trp moderately reduced plasma glucose compared with control (p < 0.05). C12+Trp, but not C12 or Trp, stimulated insulin and increased the insulin-to-glucose ratio (p < 0.05). There was no effect on plasma glucagon. In conclusion, combined intraduodenal administration of C12 and Trp reduced fasting glucose in healthy men, and this decrease was driven primarily by C12. The effects of these nutrients on postprandial blood glucose and elevated fasting blood glucose in type 2 diabetes warrant evaluation.Christina McVeay, Penelope C. E. Fitzgerald, Michael Horowitz and Christine Feinle-Bisse

Effects of intraduodenal infusions of L-phenylalanine and L-glutamine on antropyloroduodenal motility and plasma cholecystokinin in healthy men

BACKGROUND/AIMS Dietary proteins have potent eating-inhibitory and glucose-lowering effects, which may be mediated via effects of amino acids on gastrointestinal hormone and motor function, although little information is available. We have now evaluated the effects of L-phenylalanine (L-Phe) and L-glutamine (L-Gln) on antropyloroduodenal motility and plasma cholecystokinin (CCK) concentrations. METHODS Two double-blind, 3-way cross-over studies were performed, each including 10 healthy, normal-weight men. We determined the antropyloroduodenal motor and plasma CCK responses to 90-minute intraduodenal infusions of L-Phe (study A) or L-Gln (study B), each at 0.15 kcal/min (total 13.5 kcal), or 0.45 kcal/min (total 40.5 kcal), or saline (control), in randomized fashion. RESULTS Intraduodenal L-Phe at 0.45 kcal/min, but not at 0.15 kcal/min, suppressed antral (P < 0.01), and stimulated phasic (P < 0.01), but not tonic, pyloric, or duodenal pressures, while L-Phe at both 0.15 kcal/min and 0.45 kcal/min stimulated plasma CCK. In contrast, L-Gln had no effect on antral, duodenal or pyloric pressures, or plasma CCK. CONCLUSIONS Intraduodenal infusions of L-Phe and L-Gln, in doses of 0.15 kcal/min and 0.45 kcal/min for 90 minutes, have different effects on antropyloroduodenal motility and CCK in normal-weight men. The modulation of antral and pyloric pressures and CCK may contribute to the eating-inhibitory effects of oral L-Phe, possibly through the slowing of gastric emptying.Robert E Steinert, Maria F Landrock, Michael Horowitz, and Christine Feinle-Bisse

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

Accepted: 8 August 2016We 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.Gudrun Schober, Kylie Lange, Robert E. Steinert, Amy T. Hutchison, Natalie D. Luscombe-Marsh, Maria F. Landrock, Michael Horowitz, Radhika V. Seimon and Christine Feinle-Bisse

Effects of intraduodenal or intragastric administration of a bitter hop extract (Humulus lupulus L.), on upper gut motility, gut hormone secretion and energy intake in healthy-weight men

Gastrointestinal functions, particularly pyloric motility and the gut hormones, cholecystokinin and peptide YY, contribute to the regulation of acute energy intake. Bitter tastants modulate these functions, but may, in higher doses, induce GI symptoms. The aim of this study was to evaluate the effects of both dose and delivery location of a bitter hop extract (BHE) on antropyloroduodenal pressures, plasma cholecystokinin and peptide YY, appetite perceptions, gastrointestinal symptoms and energy intake in healthy-weight men. The study consisted of two consecutive parts, with part A including n = 15, and part B n = 11, healthy, lean men (BMI 22.6 ± 1.1 kg/m2 , aged 25 ± 3 years). In randomised, double-blind fashion, participants received in part A, BHE in doses of either 100 mg (“ID-BHE-100”) or 250 mg (“ID-BHE-250”), or vehicle (canola oil; “ID-control”) intraduodenally, or in part B, 250 mg BHE (“IG-BHE-250”) or vehicle (“IG-control”) intragastrically. Antropyloroduodenal pressures, hormones, appetite and symptoms were measured for 180 min, energy intake from a standardised buffet-meal was quantified subsequently. ID-BHE-250, but not ID-BHE-100, had modest, and transient, effects to stimulate pyloric pressures during the first 90 min (P < 0.05), and peptide YY from t = 60 min (P < 0.05), but did not affect antral or duodenal pressures, cholecystokinin, appetite, gastrointestinal symptoms or energy intake. IG-BHE-250 had no detectable effects. In conclusion, BHE, when administered intraduodenally, in the selected higher dose, modestly affected some appetite-related gastrointestinal functions, but had no detectable effects when given in the lower dose or intragastrically. Thus, BHE, at none of the doses or routes of administration tested, has appetite- or energy intake-suppressant effects.Vida Bitarafan, Penelope C.E. Fitzgerald, Sally D. Poppitt, John R. Ingram, Christine Feinle-Bisse

Comparative effects of small intestinal glucose on blood pressure, heart rate, and noradrenaline responses in obese and healthy subjects

Meal consumption leads to an increase in sympathetic output to compensate for hemodynamic changes and maintain blood pressure (BP). Obesity is associated with a blunting of the sympathetic response to meal ingestion, but interpretation of studies investigating these responses is compromised by their failure to account for the rate of gastric emptying, which is an important determinant of postprandial cardiovascular and sympathetic responses and, in both health and obesity, exhibits a wide interindividual variation. We sought to determine the effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP, heart rate (HR), and noradrenaline responses in obese and healthy control subjects. 12 obese subjects (age 36.6 ± 3.9 years, body mass index (BMI) 36.1 ± 1.3 kg/m² ) and 23 controls (age 27.8 ± 2.4 years, BMI 22.4 ± 0.5 kg/m² ) received intraduodenal infusions of glucose at 1 or 3 kcal/min, or saline, for 60 min (t = 0-60 min), followed by intraduodenal saline (t = 60-120 min). BP and HR were measured with an automatic cuff, and blood samples collected for measurement of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with a fall in diastolic BP in the control subjects only (P < 0.01), with no change in systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01), with no difference in responses between the groups. We conclude that cardiovascular and sympathetic responses to intraduodenal glucose infusion are comparable between obese and control subjects, and dependent on the rate of glucose delivery.Laurence G. Trahair, Tongzhi Wu, Christine Feinle-Bisset, Chinmay S. Marathe, Christopher K. Rayner, Michael Horowi and Karen L. Jone