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

2005 ◽  
Vol 289 (4) ◽  
pp. R1090-R1098 ◽  
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.

Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men

2007 ◽  
Vol 293 (3) ◽  
pp. E743-E753 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Reawika Chaikomin ◽  
Ixchel M. Brennan ◽  
Judith M. Wishart ◽  
Christopher K. Rayner ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Energy Intake ◽  
Healthy Subjects ◽  
Gastrointestinal Hormones ◽  
Saline Control ◽  
Gastrointestinal Hormone ◽  
Double Blind ◽  
Glucagon Like Peptide 1 ◽  
Glucose Plasma

Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 (“G1”), 2) 2 (“G2”), and 3) 4 (“G4”) kcal/min or of 4) saline (“control”) were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions ( P < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 ( P < 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load ( r > 0.82, P < 0.05). All glucose infusions suppressed antral ( P < 0.05), but only G4 decreased duodenal, pressure waves ( P < 0.01), resulted in a sustained stimulation of basal pyloric pressure ( P < 0.01), and decreased energy intake ( P < 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes.

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

2004 ◽  
Vol 287 (3) ◽  
pp. R524-R533 ◽  
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.

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

2019 ◽  
Vol 109 (5) ◽  
pp. 1335-1343 ◽  
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.

Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men

2005 ◽  
Vol 288 (6) ◽  
pp. R1477-R1485 ◽  
Author(s):  
Ixchel M. Brennan ◽  
Kate L. Feltrin ◽  
Michael Horowitz ◽  
Andre J. P. M. Smout ◽  
James H. Meyer ◽  
...  
Keyword(s):  
Energy Intake ◽  
Synergistic Effects ◽  
Isotonic Saline ◽  
Saline Control ◽  
Pressure Waves ◽  
Double Blind ◽  
Healthy Men ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Desire To Eat

There is evidence that CCK and glucagon-like peptide-1 (GLP-1) mediate the effects of nutrients on appetite and gastrointestinal function and that their interaction may be synergistic. We hypothesized that intravenous CCK-8 and GLP-1 would have synergistic effects on appetite, energy intake, and antropyloroduodenal (APD) motility. Nine healthy males (age 22 ± 1 yr) were studied on four separate days in a double-blind, randomized fashion. Appetite and APD pressures were measured during 150-min intravenous infusions of 1) isotonic saline (control), 2) CCK-8 (1.8 pmol·kg−1·min−1), 3) GLP-1 (0.9 pmol·kg−1·min−1), or 4) both CCK-8 (1.8 pmol·kg−1·min−1) and GLP-1 (0.9 pmol·kg−1·min−1). At 120 min, energy intake at a buffet meal was quantified. CCK-8, but not GLP-1, increased fullness, decreased desire to eat and subsequent energy intake, and increased the number and amplitude of isolated pyloric pressure waves and basal pyloric pressure ( P < 0.05). Both CCK-8 and GLP-1 decreased the number of antral and duodenal pressure waves (PWs) ( P < 0.05), and CCK-8+GLP-1 decreased the number of duodenal PWs more than either CCK-8 or GLP-1 alone ( P < 0.02). This was not the case for appetite or isolated pyloric PWs. In conclusion, at the doses evaluated, exogenously administered CCK-8 and GLP-1 had discrepant effects on appetite, energy intake, and APD pressures, and the effects of CCK-8+GLP-1, in combination, did not exceed the sum of the effects of CCK-8 and GLP-1, providing no evidence of synergism.

Effects of load, and duration, of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men

2006 ◽  
Vol 290 (3) ◽  
pp. R668-R677 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Tanya J. Little ◽  
Ixchel M. Brennan ◽  
James H. Meyer ◽  
Judith M. Wishart ◽  
...  
Keyword(s):  
Energy Intake ◽  
Peptide Yy ◽  
Pressure Waves ◽  
Double Blind ◽  
Lipid Infusion ◽  
Healthy Men ◽  
Intraduodenal Infusion ◽  
Gut Hormone ◽  
Small Intestinal ◽  
Infusion Period

Enterally administered lipid modulates antropyloroduodenal motility, gut hormone release, appetite, and energy intake. We hypothesized that these effects would be dependent on both the load, and duration, of small intestinal exposure to lipid. Eleven healthy men were studied on four occasions in a double-blind, randomized, fashion. Antropyloroduodenal motility, plasma CCK and peptide YY (PYY) concentrations, and appetite perceptions were measured during intraduodenal infusion of lipid (Intralipid) at 1) 1.33 kcal/min for 50 min, 2) 4 kcal/min for 50 min, and 3) 1.33 kcal/min for 150 min, or 4) saline for 150 min. Immediately after the infusions, energy intake was quantified. Pressure wave sequences (PWSs) were suppressed, and basal pyloric pressure, isolated pyloric pressure waves (IPPWs), plasma CCK and PYY stimulated (all P < 0.05), during the first 50 min of lipid infusion, in a load-dependent fashion. The effect of the 4 kcal/min infusion was sustained so that the suppression of antral pressure waves (PWs) and PWSs and increase in PYY remained evident after cessation of the infusion (all P < 0.05). The prolonged lipid infusion (1.33 kcal/min for 150 min) suppressed antral PWs, stimulated CCK and PYY and basal pyloric pressure (all P < 0.05), and tended to stimulate IPPWs when compared with saline throughout the entire infusion period. There was no significant effect of any of the lipid infusions on appetite or energy intake, although nausea was slightly higher ( P < 0.05) with the 4 kcal/min infusion. In conclusion, both the load, and duration, of small intestinal lipid influence antropyloroduodenal motility and patterns of CCK and PYY release.

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

2020 ◽  
Vol 318 (4) ◽  
pp. R790-R798 ◽  
Author(s):  
Christina McVeay ◽  
Robert E. Steinert ◽  
Penelope C. E. Fitzgerald ◽  
Sina S. Ullrich ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Energy Intake ◽  
Lauric Acid ◽  
Gut Hormones ◽  
Double Blind ◽  
Intraduodenal Infusion ◽  
Combined Administration ◽  
Plasma Cholecystokinin ◽  
Reduce Energy Intake ◽  
Mean Concentration ◽  
Stimulation Of

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.

scholarly journals Reproducibility of energy intake, gastric emptying, blood glucose, plasma insulin and cholecystokinin responses in healthy young males

2008 ◽  
Vol 101 (7) ◽  
pp. 1094-1102 ◽  
Author(s):  
Nivasinee S. Nair ◽  
Ixchel M. Brennan ◽  
Tanya J. Little ◽  
Diana Gentilcore ◽  
Trygve Hausken ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Energy Intake ◽  
Plasma Insulin ◽  
Intraclass Correlation ◽  
Young Male ◽  
Gastrointestinal Hormone ◽  
Hormone Release ◽  
Intraindividual Variation ◽  
Glucose Plasma

Gastric emptying, as well as intragastric meal distribution, and gastrointestinal hormones, including cholecystokinin (CCK), play an important role in appetite regulation. The evaluation of gastrointestinal factors regulating food intake is commonly performed in healthy, lean, young male participants. It has, however, been suggested that there is a marked interindividual variability in the effects of nutrient ‘preloads’ on energy intake in this group. Whether there is significant intraindividual variation in acute energy intake after a nutrient preload, and, if so, how this relates to day-to-day differences in gastric emptying and gastrointestinal hormone release, is unclear. The purpose of the present paper is to evaluate the hypothesis that energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying, intragastric distribution and gastrointestinal hormone release. Fifteen healthy men (age 25 (sem5) years) consumed a glucose preload (50 g glucose in 300 ml water; 815 kJ) on three occasions. Gastric emptying and intragastric meal distribution (using three-dimensional ultrasound), blood glucose, plasma insulin and CCK concentrations and appetite perceptions were evaluated over 90 min, and energy intake from a cold buffet-style meal was then quantified. Energy intake was highly reproducible within individuals between visits (intraclass correlation coefficient,ri = 0·9). Gastric emptying, intragastric meal distribution, blood glucose, plasma insulin and CCK concentrations and appetite perceptions did not differ between visits (ri>0·7 for all). In healthy males, energy intake is highly reproducible, at least in the short term, and is associated with reproducible patterns of gastric emptying, glycaemia, insulinaemia and CCK release.

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

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 99 ◽  
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.

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

2011 ◽  
Vol 106 (11) ◽  
pp. 1757-1762 ◽  
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.

Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index

2014 ◽  
Vol 307 (10) ◽  
pp. G958-G967 ◽  
Author(s):  
Tanya J. Little ◽  
Nicole J. Isaacs ◽  
Richard L. Young ◽  
Raffael Ott ◽  
Nam Q. Nguyen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cell Density ◽  
Energy Intake ◽  
Body Mass ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Inverse Correlation ◽  
Duodenal Mucosa ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide 1

Fatty acids (FAs) stimulate the secretion of gastrointestinal hormones, including cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1), which suppress energy intake. In obesity, gastrointestinal responses to FAs are attenuated. Recent studies have identified a key role for the FA-sensing receptors cluster of differentiation (CD)36, G protein-coupled receptor (GPR)40, GPR120, and GPR119 in mediating gastrointestinal hormone secretion. This study aimed to determine the expression and localization of these receptors in the duodenum of humans and to examine relationships with obesity. Duodenal mucosal biopsies were collected from nine lean [body mass index (BMI): 22 ± 1 kg/m2], six overweight (BMI: 28 ± 1 kg/m2), and seven obese (BMI: 49 ± 5 kg/m2) participants. Absolute levels of receptor transcripts were quantified using RT-PCR, while immunohistochemistry was used for localization. Transcripts were expressed in the duodenum of lean, overweight, and obese individuals with abundance of CD36>>GPR40>GPR120>GPR119. Expression levels of GPR120 ( r = 0.46, P = 0.03) and CD36 ( r = 0.69, P = 0.0004) were directly correlated with BMI. There was an inverse correlation between expression of GPR119 with BMI ( r2 = 0.26, P = 0.016). Immunolabeling studies localized CD36 to the brush border membrane of the duodenal mucosa and GPR40, GPR120, and GPR119 to enteroendocrine cells. The number of cells immunolabeled with CCK ( r = −0.54, P = 0.03) and GLP-1 ( r = −0.49, P = 0.045) was inversely correlated with BMI, such that duodenal CCK and GLP-1 cell density decreased with increasing BMI. In conclusion, CD36, GPR40, GPR120, and GPR119 are expressed in the human duodenum. Transcript levels of duodenal FA receptors and enteroendocrine cell density are altered with increasing BMI, suggesting that these changes may underlie decreased gastrointestinal hormone responses to fat and impaired energy intake regulation in obesity.

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