Antropyloroduodenal Pressures Research Articles

Intraduodenal calcium enhances the effects of L-tryptophan to stimulate gut hormone secretion and suppress energy intake in healthy males: a randomized, crossover, clinical trial

BackgroundIn humans, intraduodenal infusion of L-tryptophan (Trp) increases plasma concentrations of gastrointestinal hormones and stimulates pyloric pressures, both key determinants of gastric emptying and associated with potent suppression of energy intake. The stimulation of gastrointestinal hormones by Trp has been shown, in preclinical studies, to be enhanced by extracellular calcium and mediated in part by the calcium-sensing receptor. ObjectivesThis study aim was to determine whether intraduodenal calcium can enhance the effects of Trp to stimulate gastrointestinal hormones and pyloric pressures and, if so, whether it is associated with greater suppression of energy intake, in healthy males. MethodsFifteen males with normal weight (mean ± standard deviation; age: 26 ± 7 years; body mass index: 22 ± 2 kg/m2), received on 3 separate occasions, 150-min intraduodenal infusions of 0, 500, or 1000 mg calcium (Ca), each combined with Trp (load: 0.1 kcal/min, with submaximal energy intake-suppressant effects) from t = 75–150 min, in a randomized, double-blind, crossover study. Plasma concentrations of GI hormones [gastrin, cholecystokinin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide (GLP)-1, and peptide tyrosine-tyrosine (PYY)], and Trp and antropyloroduodenal pressures were measured throughout. Immediately postinfusions (t = 150–180 min), energy intake at a standardized buffet-style meal was quantified. ResultsIn response to calcium alone, both 500- and 1000-mg doses stimulated PYY, while only the 1000-mg dose stimulated GLP-1 and pyloric pressures (all P < 0.05). The 1000-mg dose also enhanced the effects of Trp to stimulate cholecystokinin and GLP-1, and both doses stimulated PYY but, surprisingly, reduced the stimulation of GIP (all P < 0.05). Both doses substantially and dose dependently enhanced the effects of Trp to suppress energy intake (Ca-0+Trp: 1108 ± 70 kcal; Ca-500+Trp: 961 ± 90 kcal; and Ca-1000+Trp: 922 ± 96 kcal; P < 0.05). ConclusionsIntraduodenal administration of calcium enhances the effect of Trp to stimulate plasma cholecystokinin, GLP-1, and PYY and suppress energy intake in healthy males. These findings have potential implications for novel nutrient-based approaches to energy intake regulation in obesity.The trial was registered at the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12620001294943).

The herbal preparation, STW5-II, reduces proximal gastric tone and stimulates antral pressures in healthy humans.

The herbal preparation, STW5-II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5-II on esophago-gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut-brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. STW5-II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double-blind, randomized fashion, on two separate occasions, separated by 3-7 days, to evaluate effects on (i) esophago-gastric junction pressures following a standardized meal using solid-state high-resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high-resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). STW5-II increased maximum intrabag volume (ml; STW5-II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago-gastric junction, pyloric, or duodenal pressures. STW5-II has marked region-specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia.

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.

Quinine Effects on Gut and Pancreatic Hormones and Antropyloroduodenal Pressures in Humans-Role of Delivery Site and Sex.

ContextThe bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be higher in the duodenum than the stomach, direct delivery to the duodenum may be more potent in stimulating these functions. The gastrointestinal responses to bitter compounds may also be modified by sex.BackgroundWe have characterized the effects of intragastric (IG) versus intraduodenal (ID) administration of quinine hydrochloride (QHCl) on gut and pancreatic hormones and antropyloroduodenal pressures in healthy men and women.Methods14 men (26 ± 2 years, BMI: 22.2 ± 0.5 kg/m2) and 14 women (28 ± 2 years, BMI: 22.5 ± 0.5 kg/m2) received 600 mg QHCl on 2 separate occasions, IG or ID as a 10-mL bolus, in randomized, double-blind fashion. Plasma ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1 (GLP-1), insulin, glucagon, and glucose concentrations and antropyloroduodenal pressures were measured at baseline and for 120 minutes following QHCl.ResultsSuppression of ghrelin (P = 0.006), stimulation of cholecystokinin (P = 0.030), peptide YY (P = 0.017), GLP-1 (P = 0.034), insulin (P = 0.024), glucagon (P = 0.030), and pyloric pressures (P = 0.050), and lowering of glucose (P = 0.001) were greater after ID-QHCl than IG-QHCl. Insulin stimulation (P = 0.021) and glucose reduction (P = 0.001) were greater in females than males, while no sex-associated effects were found for cholecystokinin, peptide YY, GLP-1, glucagon, or pyloric pressures.ConclusionID quinine has greater effects on plasma gut and pancreatic hormones and pyloric pressures than IG quinine in healthy subjects, consistent with the concept that stimulation of small intestinal bitter receptors is critical to these responses. Both insulin stimulation and glucose lowering were sex-dependent.

Effects of intraduodenal coadministration of lauric acid and leucine on gut motility, plasma cholecystokinin, and energy intake in healthy men.

The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P < 0.05). C12+Leu and C12 reduced energy intake (P < 0.05), and there was a trend for Leu to reduce (P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.

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

Background/AimsNutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation) contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shown in cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressed throughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. This study aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energy intake.MethodsFourteen healthy, lean men (25 ± 5 years; BMI: 22.5 ± 2.0 kg/m2) received on 4 separate occasions, in randomized, double-blind fashion, 60-minute intraduodenal infusions of quinine hydrochloride at doses totaling 37.5 mg (“Q37.5”), 75 mg (“Q75”) or 225 mg (“Q225”), or control (all 300 mOsmol). Antropyloroduodenal pressures (high-resolution manometry), plasma CCK (radioimmunoassay), and appetite perceptions/gastrointestinal symptoms (visual analog questionnaires) were measured. Ad libitum energy intake (buffet-meal) was quantified immediately post-infusion. Oral quinine taste-thresholds were assessed on a separate occasion using 3-alternative forced-choice procedure.ResultsAll participants detected quinine orally (detection-threshold: 0.19 ± 0.07 mmol/L). Intraduodenal quinine did not affect antral, pyloric or duodenal pressures, plasma CCK (pmol/L [peak]; control: 3.6 ± 0.4, Q37.5: 3.6 ± 0.4, Q75: 3.7 ± 0.3, Q225: 3.9 ± 0.4), appetite perceptions, gastrointestinal symptoms or energy intake (kcal; control: 1088 ± 90, Q37.5: 1057 ± 69, Q75: 1029 ±70, Q225: 1077 ± 88).ConclusionQuinine, administered intraduodenally over 60 minutes, even at moderately high doses, but low infusion rates, does not modulate appetite-related gastrointestinal functions or energy intake.

Effects of intraduodenal administration of lauric acid and L-tryptophan, alone and combined, on gut hormones, pyloric pressures, and energy intake in healthy men

The fatty acid, lauric acid ('C12'), and the amino acid, L-tryptophan ('Trp'), modulate gastrointestinal functions including gut hormones and pyloric pressures, which are important for the regulation of energy intake, and both potently suppress energy intake. We hypothesized that the intraduodenal administration of C12 and Trp, at loads that do not affect energy intake individually, when combined will reduce energy intake, which is associated with greater modulation of gut hormones and pyloric pressures. Sixteen healthy, lean males (age: 24±1.5 y) received 90-min intraduodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12+Trp (0.4 kcal/min), in a randomized, double-blind, cross-over study. Antropyloroduodenal pressures were measured continuously, and plasma cholecystokinin (CCK), ghrelin, and glucagon-like peptide-1 (GLP-1) concentrations, appetite perceptions, and gastrointestinal symptoms at 15-min intervals. Immediately after the infusions, energy intake from a standardized buffet meal was quantified. C12+Trp markedly reduced energy intake (kcal; control: 1,232±72, C12: 1,180±82, Trp: 1,269±73, C12+Trp: 1,056±106), stimulated plasma CCK (AUC(area under the curve)0-90 min, pmol/L*min; control: 21±8; C12: 129±15; Trp: 97±16; C12+Trp: 229±22) and GLP-1 (AUC0-90 min, pmol/L*min; control: 102±41; C12: 522±102; Trp: 198±63; C12+Trp: 545±138), and suppressed ghrelin (AUC0-90 min, pg/mL*min; control: -3,433±2,647; C12: -11,825±3,521; Trp: -8,417±3,734; C12+Trp: -18,188±4,165) concentrations, but did not stimulate tonic, or phasic, pyloric pressures, compared with the control (all P<0.05), or have adverse effects. C12 and Trp each stimulated CCK (P<0.05), but to a lesser degree than C12+Trp, and did not suppress energy intake or ghrelin. C12, but not Trp, stimulated GLP-1 (P<0.05) and phasic pyloric pressures (P<0.05), compared with the control. The combined intraduodenal administration of C12 and Trp, at loads that individually do not affect energy intake, substantially reduces energy intake, which is associated with a marked stimulation of CCK and suppression of ghrelin. The study was registered as a clinical trial at the Australian and New Zealand Clinical Trial Registry (www.anzctr.org.au,) as 12613000899741.

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

Whey protein is rich in the branched-chain amino acids, L-leucine, L-isoleucine and L-valine. Thus, branched-chain amino acids may, at least in part, mediate the effects of whey to reduce energy intake and/or blood glucose. Notably, 10 g of either L-leucine or L-isoleucine, administered intragastrically before a mixed-nutrient drink, lowered postprandial blood glucose, and intraduodenal infusion of L-leucine (at a rate of 0.45 kcal/min, total: 9.9 g) lowered fasting blood glucose and reduced energy intake from a subsequent meal. Whether L-valine affects energy intake, and the gastrointestinal functions involved in the regulation of energy intake, as well as blood glucose, in humans, is currently unknown. We investigated the effects of intraduodenally administered L-valine on antropyloroduodenal pressures, plasma cholecystokinin, blood glucose and energy intake. Twelve healthy lean men (age: 29 ± 2 years, BMI: 22.5 ± 0.7 kg/m2) were studied on 3 separate occasions in randomised, double-blind order. Antropyloroduodenal pressures, plasma cholecystokinin, blood glucose, appetite perceptions and gastrointestinal symptoms were measured during 90-min intraduodenal infusions of L-valine at 0.15 kcal/min (total: 3.3 g) or 0.45 kcal/min (total: 9.9 g), or 0.9% saline (control). Energy intake from a buffet-meal immediately after the infusions was quantified. L-valine did not affect antral, pyloric (mean number; control: 14 ± 5; L-Val-0.15: 21 ± 9; L-Val-0.45: 11 ± 4), or duodenal pressures, plasma cholecystokinin (mean concentration, pmol/L; control: 3.1 ± 0.3; L-Val-0.15: 3.2 ± 0.3; L-Val-0.45: 3.0 ± 0.3), blood glucose, appetite perceptions, symptoms or energy intake (kcal; control: 1040 ± 73; L-Val-0.15: 1040 ± 81; L-Val-0.45: 1056 ± 100), at either load (p > 0.05 for all). In conclusion, intraduodenal infusion of L-valine, at loads that are moderately (3.3 g) or substantially (9.9 g) above World Health Organization valine requirement recommendations, does not appear to have energy intake- or blood glucose-lowering effects.

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

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.

Comparative effects of intraduodenal whey protein hydrolysate on antropyloroduodenal motility, gut hormones, glycemia, appetite, and energy intake in lean and obese men

In lean individuals, intraduodenal protein and lipid modulate gastrointestinal motor and hormone functions and reduce energy intake in a load-dependent manner; protein also stimulates insulin, with modest effects on reducing blood glucose. The effect of intraduodenal lipid on gastrointestinal motor and hormone responses is diminished in obesity; whether the effects of protein are also attenuated remains unclear. The objectives of this study were to characterize the load-dependent effects of intraduodenal whey protein hydrolysate on antropyloroduodenal pressures, gut hormones, glycemia, appetite, and energy intake in obese subjects and to compare the responses to the higher protein load with those in lean subjects. We measured antropyloroduodenal pressures, plasma cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, blood glucose, appetite, and energy intake in 12 nondiabetic obese men on 3 separate occasions, in a double-blind, randomized order, during 60-min intraduodenal infusions of hydrolyzed whey protein at either 0 (saline control), 1.5, or 3 kcal/min. Twelve age-matched lean individuals received a 3-kcal/min infusion only. Immediately after the infusions, energy intake from a buffet lunch was quantified. In obese subjects, protein suppressed antral and duodenal pressures; stimulated plasma CCK, GLP-1, GIP, insulin, and glucagon (all r > 0.57, P < 0.01); and tended to reduce energy intake (r = -10.38, P = 0.057) in a dose-dependent manner. In response to the 3-kcal/min protein load, antropyloroduodenal pressures, CCK, GLP-1, and glucagon did not differ between lean and obese subjects. Insulin release was greater, and GIP release less, in obese than in lean subjects (both P < 0.05), whereas the reduction in glucose was comparable. Energy intake tended to be higher in obese subjects (P = 0.08). The gastrointestinal effects of hydrolyzed whey protein remain relatively intact in obesity; however, the observed changes in insulin and GIP suggest early disturbances in the insulin-incretin axis. This study was registered at www.anzctr.org.au as ACTRN 12612000203853.

Effects of acute and longer-term dietary restriction on upper gut motility, hormone, appetite, and energy-intake responses to duodenal lipid in lean and obese men

A 4-d 70% energy restriction enhances gastrointestinal sensitivity to nutrients associated with enhanced energy-intake suppression by lipid. To our knowledge, it is unknown whether these changes occur with 30% energy restriction and are sustained in the longer term. We hypothesized that 1) a 4-d 30% energy restriction would enhance effects of intraduodenal lipid on gastrointestinal motility, gut hormones, appetite, and energy intake in lean and obese men and 2) a 12-wk energy restriction associated with weight loss would diminish effects of acute energy restriction on responses to lipid in in obese men. Twelve obese males were studied before (day 0) and after 4 d (day 5), 4 wk (week 4), and 12 wk (week 12), and 12 lean males were studied before and after 4 d of consumption of a 30% energy-restricted diet. On each study day, antropyloroduodenal pressures, gut hormones, and appetite during a 120-min (2.86-kcal/min) intraduodenal lipid infusion and energy intake at a buffet lunch were measured. On day 5, fasting cholecystokinin was less, and ghrelin was higher, in lean (P < 0.05) but not obese men, and lipid-stimulated cholecystokinin and peptide YY and the desire to eat were greater in both groups (P < 0.05), with no differences in energy intakes compared with on day 0. In obese men, a 12-wk energy restriction led to weight loss (9.7 ± 0.7 kg). Lipid-induced basal pyloric pressures (BPPs), peptide YY, and the desire to eat were greater (P < 0.05), whereas the amount eaten was less (P < 0.05), at weeks 4 and 12 compared with day 0. A 4-d 30% energy restriction modestly affects responses to intraduodenal lipid in health and obesity but not energy intake, whereas a 12-wk energy restriction, associated with weight-loss, enhances lipid-induced BPP and peptide YY and reduces food intake, suggesting that energy restriction increases gastrointestinal sensitivity to lipid. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as 12609000943246.

Effects of Intraduodenal Glutamine on Incretin Hormone and Insulin Release, the Glycemic Response to an Intraduodenal Glucose Infusion, and Antropyloroduodenal Motility in Health and Type 2 Diabetes

OBJECTIVEGlutamine reduces postprandial glycemia when given before oral glucose. We evaluated whether this is mediated by stimulation of insulin and/or slowing of gastric emptying.RESEARCH DESIGN AND METHODSTen healthy subjects were studied during intraduodenal (ID) infusion of glutamine (7.5 or 15 g) or saline over 30 min, followed by glucose (75 g over 100 min), while recording antropyloroduodenal pressures. Ten patients with type 2 diabetes mellitus (T2DM) were also studied with 15 g glutamine or saline.RESULTSID glutamine stimulated glucagon-like peptide 1 (GLP-1; healthy: P < 0.05; T2DM: P < 0.05), glucose-dependent insulinotropic polypeptide (GIP; P = 0.098; P < 0.05), glucagon (P < 0.01; P < 0.001), insulin (P = 0.05; P < 0.01), and phasic pyloric pressures (P < 0.05; P < 0.05), but did not lower blood glucose (P = 0.077; P = 0.5).CONCLUSIONSGlutamine does not lower glycemia after ID glucose, despite stimulating GLP-1, GIP, and insulin, probably due to increased glucagon. Its capacity for pyloric stimulation suggests that delayed gastric emptying is a major mechanism for lowering glycemia when glutamine is given before oral glucose.

Intraduodenal protein modulates antropyloroduodenal motility, hormone release, glycemia, appetite, and energy intake in lean men

Intraduodenal fat and carbohydrate modulate antropyloroduodenal motility and hormone release and suppress appetite and energy intake in a load-dependent manner. Protein also suppresses energy intake, but its effects on these gastrointestinal factors and their role in the appetite-suppressive effects of protein remain unclear. We aimed to characterize the effects of different intraduodenal protein loads on antropyloroduodenal pressures, gastrointestinal hormone release, glucose and insulin concentrations, appetite perceptions, and energy intake. Sixteen lean, healthy men were studied on 4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures, plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin, blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline (control). Energy intakes at a buffet lunch consumed immediately after the infusion were quantified. Increases in the load of protein resulted in greater suppression of antral motility, greater stimulation of basal and isolated pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and greater suppression of energy intake. However, energy intake was reduced only after a protein load of 3 kcal/min compared with after all other treatments (P < 0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP-1, and insulin was related inversely with basal pyloric pressure (r = -0.51, P < 0.001). The acute effects of intraduodenal protein on antropyloroduodenal motility, gastrointestinal hormone release, glucose, and insulin are load dependent and contribute to the suppression of energy intake. This trial was registered at www.anzctr.org.au as 12610000376044.

Marked differences in gustatory and gastrointestinal sensitivity to oleic acid between lean and obese men

Both orosensory stimulation and feedback from the gastrointestinal tract contribute to energy intake regulation. We evaluated the hypothesis that overweight or obese subjects would be less sensitive to both oral and intraduodenal oleic acid exposure than would lean subjects. Eleven overweight or obese and 8 lean men were studied on 2 occasions, during which antropyloroduodenal pressures, plasma cholecystokinin and peptide YY, and appetite were measured during 90-min intraduodenal infusions of saline or oleic acid (18:1 load: 0.78 kcal/min); energy intake (buffet lunch) was determined immediately afterward. Oral detection thresholds for 18:1 and recent dietary intake (2-d recall) were also quantified. In lean subjects, the number of isolated pyloric pressure waves (IPPWs) was greater during 18:1 infusion than during saline infusion (P < 0.05); no significant differences were observed between the 18:1 and saline infusions in the overweight or obese subjects. In both groups, 18:1 stimulated plasma cholecystokinin and peptide YY and suppressed energy intake compared with saline (P < 0.05), with trends for reduced cholecystokinin and energy intake responses in the overweight or obese subjects. Detection thresholds for 18:1 were greater in overweight or obese (7.9 ± 0.1 mmol/L) than in lean (4.1 ± 0.4 mmol/L) subjects (P < 0.05). Overweight or obese subjects had greater recent energy (P < 0.05) and fat (P = 0.07) intakes than did lean subjects. There was a direct relation (r = 0.669) of body mass index with 18:1 detection thresholds and inverse relations (r < -0.51) of IPPWs with body mass index and 18:1 detection thresholds (P < 0.05). The ability to detect oleic acid both orally and within the gastrointestinal tract is compromised in obese men, and oral and gastrointestinal responses to oleic acid are related. This trial was registered at www.actr.org.au (Australian New Zealand Clinical Trials Registry) as 12609000557235.

Pooled-data analysis identifies pyloric pressures and plasma cholecystokinin concentrations as major determinants of acute energy intake in healthy, lean men

The interaction of nutrients with the small intestine modulates gastropyloroduodenal motility, stimulates the release of gut hormones, and suppresses appetite and energy intake. We evaluated which, if any, of these variables are independent determinants of acute energy intake in healthy, lean men. We pooled data from 8 published studies that involved a total of 67 healthy, lean men in whom antropyloroduodenal pressures, gastrointestinal hormones, and perceptions were measured during intraduodenal nutrient or intravenous hormone infusions. In all of the studies, the energy intake at a buffet lunch was quantified immediately after the infusions. To select specific motor, hormone, or perception variables for inclusion in a multivariable mixed-effects model for determination of independent predictors of energy intake, we assessed all variables for collinearity and determined within-subject correlations between energy intake and these variables by using bivariate analyses adjusted for repeated measures. Although correlations were shown between energy intake and antropyloroduodenal pressures, plasma hormone concentrations, and gastrointestinal perceptions, only the peak number of isolated pyloric-pressure waves, peak plasma cholecystokinin concentration, and area under the curve of nausea were identified as independent predictors of energy intake (all P < 0.05), so that increases of 1 pressure wave, 1 pmol/L, and 1 mm . min were associated with reductions in energy intake of approximately 36, approximately 88, and approximately 0.4, respectively. We identified specific changes in gastrointestinal motor and hormone functions (ie, stimulation of pyloric pressures and plasma cholecystokinin) and nausea that are associated with the suppression of acute energy intake.

The droplet size of intraduodenal fat emulsions influences antropyloroduodenal motility, hormone release, and appetite in healthy males

Background: The presence of fat in the small intestine modulates gastrointestinal motility, stimulates plasma cholecystokinin and peptide YY release, and suppresses appetite and energy intake. These effects are dependent on the lipolysis of fat.Objective: Our aim was to evaluate the hypothesis that increasing the droplet size of a fat emulsion would attenuate these effects.Design: Ten healthy, lean males were studied on 4 separate occasions in single-blind randomized order. Antropyloroduodenal pressures, plasma triglycerides, cholecystokinin, peptide YY, and appetite were measured during 120-min intraduodenal infusions of fat emulsions comprising 3 different droplet sizes: 1) 0.26 μm (LE-0.26), 2) 30 μm (LE-30), and 3) 170 μm (LE-170) in addition to saline (control). Energy intake at a buffet lunch was quantified immediately after the infusions.Results: Increasing the droplet size of the lipid emulsion was associated with diminished suppression of antral (r = 0.75, P < 0.01) and duodenal (r = 0.80, P < 0.01) pressure waves and with stimulation of isolated (r = –0.72, P < 0.01) and basal (r = –0.83, P < 0.01) pyloric pressures. Increasing the droplet size was also associated with attenuation of the stimulation of plasma triglycerides (r = –0.73, P < 0.001), cholecystokinin (r = –0.73, P < 0.001), and peptide YY (r = –0.83, P < 0.001) as well as with reductions in the suppression of hunger (r = 0.75, P < 0.01) and energy intake (r = 0.66, P < 0.001).Conclusions: The acute effects of intraduodenal fat emulsions on gastrointestinal function and appetite are dependent on fat droplet size. These observations have implications for the design of functional foods to maximize effects on those gut functions that are involved in the suppression of appetite.

Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males

Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures (r = 0.76, P < 0.01), plasma CCK (r = 0.66, P < 0.01), and PYY (r = 0.98, P < 0.001), and reduced suppression of antral (r = -0.64, P < 0.05) and duodenal (r = -0.69, P < 0.05) pressure waves, desire-to-eat (r = -0.8, P < 0.001), and energy intake (r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

Dose-dependent effects of cholecystokinin-8 on antropyloroduodenal motility, gastrointestinal hormones, appetite, and energy intake in healthy men

CCK mediates the effects of nutrients on gastrointestinal motility and appetite. Intravenously administered CCK stimulates pyloric pressures, increases plasma PYY, and suppresses ghrelin, all of which may be important in the regulation of appetite and energy intake. The dose-related effects of exogenous CCK on gastrointestinal motility and gut hormone release, and the relationships between these effects and those on energy intake, are uncertain. We hypothesized that 1) intravenous CCK-8 would have dose-dependent effects on antropyloroduodenal (APD) pressures, plasma PYY and ghrelin concentrations, appetite, and energy intake and 2) the suppression of energy intake by CCK-8 would be related to the stimulation of pyloric motility. Ten healthy men (age 26 +/- 2 yr) were studied on four separate occasions in double-blind, randomized fashion. APD pressures, plasma PYY and ghrelin, and appetite were measured during 120-min intravenous infusions of 1) saline ("control") or 2) CCK-8 at 0.33 ("CCK0.33"), 3) 0.66 ("CCK0.66"), or 4) 2.0 ("CCK2.0") ng.kg(-1).min(-1). After 90 min, energy intake at a buffet meal was quantified. CCK-8 dose-dependently stimulated phasic and tonic pyloric pressures and plasma PYY concentrations (r > 0.70, P < 0.05) and reduced desire to eat and energy intake (r > -0.60, P < 0.05) without inducing nausea. There were relationships between basal pyloric pressure and isolated pyloric pressure waves (IPPW) with plasma CCK (r > 0.50, P < 0.01) and between energy intake with IPPW (r = -0.70, P < 0.05). Therefore, our study demonstrates that exogenous CCK-8 has dose-related effects on APD motility, plasma PYY, desire to eat, and energy intake and suggests that the suppression of energy intake is related to the stimulation of IPPW.

Comparative effects of intraduodenal infusions of lauric and oleic acids on antropyloroduodenal motility, plasma cholecystokinin and peptide YY, appetite, and energy intake in healthy men

BackgroundThe regulation of gastrointestinal function and energy intake by fatty acids depends on their chain length. Animal studies suggest that lauric acid (C12) may have more potent suppressive effects on energy intake than does oleic acid (C18). ObjectiveWe compared the effects of equicaloric loads of C12 and C18 on antropyloroduodenal (APD) motility, plasma concentrations of cholecystokinin (CCK) and peptide YY (PYY), appetite, and energy intake. DesignThirteen healthy men (aged 20–46 y) were studied on 3 occasions in double-blind, randomized fashion. APD pressure waves, plasma hormones, and appetite perceptions were measured during 60-min intraduodenal infusions of 1) C12, 2) C18, or 3) 0.9% saline as control (rate: 4 mL/min; energy load for C12 and C18: 0.4 kcal/min); between 60 and 90 min, the subjects consumed a meal. Energy intake at a buffet meal was quantified. ResultsC12 and C18 both reduced antral (P < 0.001) and duodenal (P < 0.01) pressure waves and stimulated isolated pyloric pressure waves (P < 0.01) and plasma CCK (P < 0.001), with no differences between them. Although C12 and C18 both increased basal pyloric pressure (P < 0.05), C12 had a greater effect than did C18 (P < 0.01). In contrast, although both C12 and C18 increased plasma PYY (P < 0.001), C18 had a greater effect than C12. C12, but not C18, suppressed energy intake (P < 0.05). ConclusionsAt the load administered, C12, but not C18, suppressed energy intake, and C12 was a more potent stimulant of basal pyloric pressure. These discrepant effects are not apparently accounted for by changes in CCK or PYY secretion.

Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects

Postprandial hypotension is an important clinical problem, particularly in the elderly. 5-Hydroxytryptamine3 (5-HT3) mechanisms may be important in the regulation of splanchnic blood flow and blood pressure (BP), and in mediating the effects of small intestinal nutrients on gastrointestinal motility. The aims of this study were to evaluate the effects of the 5-HT3 antagonist granisetron on the BP, heart rate (HR), and antropyloroduodenal (APD) motility responses to intraduodenal glucose in healthy older subjects. Ten subjects (5 male, 5 female, aged 65-76 yr) received an intraduodenal glucose infusion (3 kcal/min) for 60 min (t = 0-60 min), followed by intraduodenal saline for a further 60 min (t = 60-120 min) on 2 days. Granisetron (10 microg/kg) or control (saline) was given intravenously at t = -25 min. BP (systolic and diastolic), HR, and APD pressures were measured. Pressure waves in the duodenal channel closest ("local") to the infusion site were quantified separately. During intraduodenal glucose, there were falls in systolic and diastolic BP and a rise in HR (P < 0.0001 for all); granisetron had no effect on these responses. Granisetron suppressed the number and amplitude (P < 0.05 for both) of local duodenal pressures during intraduodenal glucose. Otherwise, the effects of intraduodenal glucose on APD motility did not differ between study days. We conclude that in healthy older subjects, 5-HT3 mechanisms modulate the local duodenal motor effects of, but not the cardiovascular responses to, small intestinal glucose.