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.

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

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz020 ◽

2019 ◽

Vol 109 (5) ◽

pp. 1335-1343 ◽

Cited By ~ 2

Author(s):

Christina McVeay ◽

Penelope C E Fitzgerald ◽

Sina S Ullrich ◽

Robert E Steinert ◽

Michael Horowitz ◽

...

Keyword(s):

Clinical Trial ◽

Energy Intake ◽

Lauric Acid ◽

Gastrointestinal Symptoms ◽

Area Under The Curve ◽

Gut Hormones ◽

Saline Control ◽

Clinical Trial Registry ◽

Double Blind ◽

Intraduodenal Administration

ABSTRACT Background 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. Objective 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. Design 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. Results 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. Conclusion 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.

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Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00290.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. R1090-R1098 ◽

Cited By ~ 41

Author(s):

Tanya J. Little ◽

Kate L. Feltrin ◽

Michael Horowitz ◽

Andre J. P. M. Smout ◽

Thomas Rades ◽

...

Keyword(s):

Energy Intake ◽

Lauric Acid ◽

Hormone Secretion ◽

Decanoic Acid ◽

Saline Control ◽

Gastrointestinal Hormone ◽

Pressure Waves ◽

Hormone Release ◽

Double Blind ◽

Intraduodenal Infusion

We recently reported that intraduodenal infusion of lauric acid (C12) (0.375 kcal/min, 106 mM) stimulates isolated pyloric pressure waves (IPPWs), inhibits antral and duodenal pressure waves (PWs), stimulates release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), and suppresses energy intake and that these effects are much greater than those seen in response to isocaloric decanoic acid (C10) infusion. Administration of C12 was, however, associated with nausea, confounding interpretation of the results. The aim of this study was to evaluate the effects of different intraduodenal doses of C12 on antropyloroduodenal (APD) motility, plasma CCK and GLP-1 concentrations, appetite, and energy intake. Thirteen healthy males were studied on 4 days in double-blind, randomized fashion. APD pressures, plasma CCK and GLP-1 concentrations, and appetite perceptions were measured during 90-min ID infusion of C12 at 0.1 (14 mM), 0.2 (28 mM), or 0.4 (56 mM) kcal/min or saline (control; rate 4 ml/min). Energy intake was determined at a buffet meal immediately following infusion. C12 dose-dependently stimulated IPPWs, decreased antral and duodenal motility, and stimulated secretion of CCK and GLP-1 ( r > 0.4, P < 0.05 for all). C12 (0.4 kcal/min) suppressed energy intake compared with control, C12 (0.1 kcal/min), and C12 (0.2 kcal/min) ( P < 0.05). These effects were observed in the absence of nausea. In conclusion, intraduodenal C12 dose-dependently modulated APD motility and gastrointestinal hormone release in healthy male subjects, whereas effects on energy intake were only apparent with the highest dose infused (0.4 kcal/min), possibly because only at this dose was modulation of APD motility and gastrointestinal hormone secretion sufficient for a suppressant effect on energy intake.

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Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00039.2004 ◽

2004 ◽

Vol 287 (3) ◽

pp. R524-R533 ◽

Cited By ~ 151

Author(s):

Kate L. Feltrin ◽

Tanya J. Little ◽

James H. Meyer ◽

Michael Horowitz ◽

Andre J. P. M. Smout ◽

...

Keyword(s):

Fatty Acids ◽

Chain Length ◽

Energy Intake ◽

Decanoic Acid ◽

Double Blind ◽

Intraduodenal Infusion ◽

Gut Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Intraduodenal Administration

The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19–47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions ( P < 0.001) and energy intake (control: 4,604 ± 464 kJ, C10: 4,109 ± 588 kJ, and C12: 1,747 ± 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea ( P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control ( P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs ( P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs ( P = 0.004). C12 and C10 increased plasma CCK ( P < 0.001), but the effect of C12 was substantially greater ( P = 0.001); C12 stimulated GLP-1 ( P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.

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

Nutrients ◽

10.3390/nu11010099 ◽

2019 ◽

Vol 11 (1) ◽

pp. 99 ◽

Cited By ~ 2

Author(s):

Rachel A. Elovaris ◽

Penelope C. E. Fitzgerald ◽

Vida Bitarafan ◽

Sina S. Ullrich ◽

Michael Horowitz ◽

...

Keyword(s):

Amino Acids ◽

Blood Glucose ◽

Energy Intake ◽

Branched Chain Amino Acids ◽

World Health ◽

Postprandial Blood Glucose ◽

Saline Control ◽

Intraduodenal Infusion ◽

Plasma Cholecystokinin ◽

Branched Chain

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.

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Effects of oligofructose on appetite profile, glucagon-like peptide 1 and peptide YY3-36 concentrations and energy intake

British Journal Of Nutrition ◽

10.1017/s0007114511002194 ◽

2011 ◽

Vol 106 (11) ◽

pp. 1757-1762 ◽

Cited By ~ 65

Author(s):

Sanne P. M. Verhoef ◽

Diederick Meyer ◽

Klaas R. Westerterp

Keyword(s):

Energy Intake ◽

Human Subjects ◽

Hormone Secretion ◽

Area Under The Curve ◽

Double Blind ◽

Time Treatment ◽

Satiety Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Reduce Energy Intake

In rats, oligofructose has been shown to stimulate satiety hormone secretion, reduce energy intake and promote weight loss. The present study aimed to examine the effect of oligofructose supplementation on appetite profiles, satiety hormone concentrations and energy intake in human subjects. A total of thirty-one healthy subjects (ten men and twenty-one women) aged 28 (sem 3) years with a BMI of 24·8 (sem 0·3) kg/m2 were included in a randomised double-blind, cross-over study. The subjects received 10 g oligofructose, 16 g oligofructose or 16 g placebo (maltodextrin) daily for 13 d, with a 2-week washout period between treatments. Appetite profile, active glucagon-like peptide 1 (GLP-1) and peptide YY3-36 (PYY) concentrations and energy intake were assessed on days 0 and 13 of the treatment period. Time × treatment interaction revealed a trend of reduction in energy intake over days 0–13 by oligofructose (P = 0·068). Energy intake was significantly reduced (11 %) over time on day 13 compared with day 0 with 16 g/d oligofructose (2801 (sem 301) v. 3217 (sem 320) kJ, P < 0·05). Moreover, energy intake was significantly lower with 16 g/d oligofructose compared with 10 g/d oligofructose on day 13 (2801 (sem 301) v. 3177 (sem 276) kJ, P < 0·05). Area under the curve (AUC) for GLP-1 on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose (45 (sem 4) v. 41 (sem 3) pmol/l × h, P < 0·05). In the morning until lunch, AUC0–230 min for PYY on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose and placebo (409 (sem 35) v. 222 (sem 19) and 211 (sem 20) pg/ml × h, P < 0·01). In conclusion, 16 g/d and not 10 g/d oligofructose may be an effective dose to reduce energy intake, possibly supported by higher GLP-1 and PYY concentrations.

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Acute Effects of Substitution, and Addition, of Carbohydrates and Fat to Protein on Gastric Emptying, Blood Glucose, Gut Hormones, Appetite, and Energy Intake

Nutrients ◽

10.3390/nu10101451 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1451 ◽

Cited By ~ 6

Author(s):

Caroline Giezenaar ◽

Kylie Lange ◽

Trygve Hausken ◽

Karen Jones ◽

Michael Horowitz ◽

...

Keyword(s):

Blood Glucose ◽

Gastric Emptying ◽

Olive Oil ◽

Whey Protein ◽

Energy Intake ◽

Young Men ◽

Gut Hormones ◽

Double Blind ◽

Gut Hormone ◽

G 28

Whey protein, when ingested on its own, load-dependently slows gastric emptying and stimulates gut hormone concentrations in healthy young men. The aim of this study was to determine the effects of substitution, and addition, of carbohydrate (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind order, 13 healthy young men (age: 23 ± 1 years, body mass index: 24 ± 1 kg/m2) ingested a control drink (450 mL; ~2 kcal/‘control’) or iso-volumetric drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280 kcal/‘M280′), (ii) 70 g/28 g/12.4 g (504kcal/‘M504′), and (iii) 70 g/0 g/0 g (280 kcal/‘P280′), on 4 separate study days. Gastric emptying (n = 11, 3D-ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), appetite (visual analogue scales), and ad-libitum buffet-meal energy intake (180–210 min) were determined. Substitution of protein with carbohydrate and fat was associated with faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of ghrelin, and stimulation of GLP-1 (all P < 0.001); while the addition of carbohydrate and fat to protein did not affect gastric emptying or gut hormone responses significantly. Total energy intake (i.e., drink plus meal) was greater after all caloric drinks than control (P < 0.001). In conclusion, substitution of whey protein with dextrose and olive oil accelerated gastric emptying. Higher protein content of a mixed macronutrient drink increased gut hormone and insulin responses.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90934.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. R912-R920 ◽

Cited By ~ 25

Author(s):

Radhika V. Seimon ◽

Kate L. Feltrin ◽

James H. Meyer ◽

Ixchel M. Brennan ◽

Judith M. Wishart ◽

...

Keyword(s):

Blood Glucose ◽

Energy Intake ◽

Peptide Yy ◽

Gut Hormones ◽

Double Blind ◽

Glucose Levels ◽

Gut Function ◽

Glucagon Like Peptide 1 ◽

Desire To Eat ◽

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.

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Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00478.2011 ◽

2012 ◽

Vol 303 (1) ◽

pp. G129-G140 ◽

Cited By ~ 116

Author(s):

Ixchel M. Brennan ◽

Natalie D. Luscombe-Marsh ◽

Radhika V. Seimon ◽

Bärbel Otto ◽

Michael Horowitz ◽

...

Keyword(s):

Energy Intake ◽

Peptide Yy ◽

Gastrointestinal Hormones ◽

Gut Hormones ◽

Low Protein ◽

Gut Hormone ◽

Plasma Cholecystokinin ◽

Obese Subjects ◽

Hormone Responses ◽

Protein Load

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals ( P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals ( P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

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

British Journal Of Nutrition ◽

10.1079/bjn2003971 ◽

2003 ◽

Vol 90 (5) ◽

pp. 849-852 ◽

Cited By ~ 39

Author(s):

Deirdre O'Donovan ◽

Christine Feinle-Bisset ◽

Judith Wishart ◽

Michael Horowitz

Keyword(s):

Energy Intake ◽

Area Under The Curve ◽

Inhibitory Effect ◽

Normal Weight ◽

Double Blind ◽

Plasma Cholecystokinin ◽

Fat Malabsorption ◽

Treatment Of Obesity ◽

Access To Food ◽

Lipase Inhibition

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 400g (2562kJ); females 300g (1923kJ)), containing orlistat (120mg) on one study day (and no orlistat on the other ‘control’ day), 30min before ad libitum access to food and drinks; energy intake was assessed during the following 8h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10220 (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 20min 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 0–510min 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.

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