Free Fatty Acids Have More Potent Effects on Gastric Emptying, Gut Hormones, and Appetite Than Triacylglycerides
2007; Elsevier BV; Volume: 133; Issue: 4 Linguagem: Inglês
10.1053/j.gastro.2007.06.060
ISSN1528-0012
AutoresTanya J. Little, Antonietta Russo, James H. Meyer, Michael Horowitz, Douglas R. Smyth, Max Bellon, Judith M. Wishart, Karen L. Jones, Christine Feinle–Bisset,
Tópico(s)Biochemical Analysis and Sensing Techniques
ResumoBackground & Aims: The effects of fat on gastric emptying (GE), gut hormones, and energy intake are dependent on digestion to free fatty acids (FFAs). In animals, small intestinal oleic acid inhibits energy intake more potently than the triacylglyceride (TG) triolein, but there is limited information about the comparative effects of FFA and TG in human beings. We compared the effects of FFA and TG on GE, gut hormone secretion, appetite, and energy intake in healthy males. Methods: Nine men (age, 23 ± 2 y; body mass index, 22 ± 1 kg/m2) were studied on 3 occasions to evaluate the effects of (1) 40 g oleic acid (FFA, 1830 kJ), (2) 40 g macadamia oil (TG, 1856 kJ; both 600-mL oil-in-water emulsions stabilized with 4% milk protein and labeled with 15 MBq 123I), or (3) 600 mL 4% milk protein (control, 352 kJ), administered intragastrically, on GE, plasma cholecystokinin (CCK) and peptide-YY (PYY) levels, appetite perceptions, and subsequent energy intake. Results: GE of FFA was much slower than that of TG (P < .05), with greater retention of FFA, than TG, in the proximal stomach (P < .001). Hunger was less (P < .05), and fullness was greater (P < .05), after FFA when compared with control and TG. Increases in plasma CCK and PYY levels were greater after FFA than TG or control (P < .05). Energy intake tended to be less after FFA compared with TG (control, 4754 ± 610 kJ; TG, 5463 ± 662 kJ; FFA, 4199 ± 410 kJ). Conclusions: FFAs empty from the stomach more slowly, but stimulate CCK and PYY and suppress appetite more potently than TG in healthy human beings. Background & Aims: The effects of fat on gastric emptying (GE), gut hormones, and energy intake are dependent on digestion to free fatty acids (FFAs). In animals, small intestinal oleic acid inhibits energy intake more potently than the triacylglyceride (TG) triolein, but there is limited information about the comparative effects of FFA and TG in human beings. We compared the effects of FFA and TG on GE, gut hormone secretion, appetite, and energy intake in healthy males. Methods: Nine men (age, 23 ± 2 y; body mass index, 22 ± 1 kg/m2) were studied on 3 occasions to evaluate the effects of (1) 40 g oleic acid (FFA, 1830 kJ), (2) 40 g macadamia oil (TG, 1856 kJ; both 600-mL oil-in-water emulsions stabilized with 4% milk protein and labeled with 15 MBq 123I), or (3) 600 mL 4% milk protein (control, 352 kJ), administered intragastrically, on GE, plasma cholecystokinin (CCK) and peptide-YY (PYY) levels, appetite perceptions, and subsequent energy intake. Results: GE of FFA was much slower than that of TG (P < .05), with greater retention of FFA, than TG, in the proximal stomach (P < .001). Hunger was less (P < .05), and fullness was greater (P < .05), after FFA when compared with control and TG. Increases in plasma CCK and PYY levels were greater after FFA than TG or control (P < .05). Energy intake tended to be less after FFA compared with TG (control, 4754 ± 610 kJ; TG, 5463 ± 662 kJ; FFA, 4199 ± 410 kJ). Conclusions: FFAs empty from the stomach more slowly, but stimulate CCK and PYY and suppress appetite more potently than TG in healthy human beings. See editorial on page 1367. See editorial on page 1367. Triacylglycerides (TGs) in the small intestine modulate gastrointestinal function and appetite. In human beings, small intestinal TGs modulate gastrointestinal motility,1Heddle R. Dent J. Read N.W. et al.Antropyloroduodenal motor responses to intraduodenal lipid infusion in healthy volunteers.Am J Physiol. 1988; 254: G671-G679PubMed Google Scholar stimulate gastrointestinal hormone release, including cholecystokinin (CCK)2MacIntosh C.G. Andrews J.M. Jones K.L. et al.Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility.Am J Clin Nutr. 1999; 69: 999-1006PubMed Scopus (206) Google Scholar and peptide-YY (PYY),3Feinle-Bisset C. Patterson M. Ghatei M.A. et al.Fat digestion is required for suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid.Am J Physiol. 2005; 289: E948-E953Google Scholar and suppress subsequent energy intake.2MacIntosh C.G. Andrews J.M. Jones K.L. et al.Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility.Am J Clin Nutr. 1999; 69: 999-1006PubMed Scopus (206) Google Scholar It has become apparent that small intestinal TG digestion, and the subsequent release of lipolytic products, is essential for these effects.4Glatzle J. Kalogeris T.J. Zittel T.T. et al.Chylomicron components mediate intestinal lipid-induced inhibition of gastric motor function.Am J Physiol. 2002; 282: G86-G91Google Scholar, 5Glatzle J. Wang Y. Adelson D.W. et al.Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor-mediated pathway to inhibit gastric motor function in the rat.J Physiol. 2003; 550: 657-664Crossref PubMed Scopus (54) Google Scholar, 6Hildebrand P. Petrig C. Burckhardt B. et al.Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release.Gastroenterology. 1998; 114: 123-129Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar For example, administration of orlistat, which blocks hydrolysis of TG, accelerates gastric emptying (GE)7Degen L. Matzinger D. Drewe J. et al.Role of free fatty acids in regulating gastric emptying and gallbladder contraction.Digestion. 2006; 74: 131-139Crossref PubMed Scopus (27) Google Scholar, 8Schwizer W. Asal K. Kreiss C. et al.Role of lipase in the regulation of upper gastrointestinal function in humans.Am J Physiol. 1997; 273: G612-G620PubMed Google Scholar, 9Pilichiewicz A. O'Donovan D. Feinle C. et al.Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus.J Clin Endocrinol Metab. 2003; 88: 3829-3834Crossref PubMed Scopus (71) Google Scholar and attenuates the effects of duodenal TG on proximal gastric relaxation10Feinle C. Rades T. Otto B. et al.Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans.Gastroenterology. 2001; 120: 1100-1107Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar; antropyloroduodenal motility11Feinle C. O'Donovan D.G. Doran S. et al.Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.Am J Physiol. 2003; 284: G798-G807Google Scholar; perceptions of fullness and energy intake11Feinle C. O'Donovan D.G. Doran S. et al.Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.Am J Physiol. 2003; 284: G798-G807Google Scholar, 12Matzinger D. Degen L. Drewe J. et al.The role of long chain fatty acids in regulating food intake and cholecystokinin release in humans.Gut. 2000; 46: 688-693Crossref PubMed Scopus (165) Google Scholar; gallbladder and pancreatic secretion6Hildebrand P. Petrig C. Burckhardt B. et al.Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release.Gastroenterology. 1998; 114: 123-129Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar; stimulation of plasma CCK, glucagon-like peptide-1, and PYY; and the suppression of ghrelin.6Hildebrand P. Petrig C. Burckhardt B. et al.Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release.Gastroenterology. 1998; 114: 123-129Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 11Feinle C. O'Donovan D.G. Doran S. et al.Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.Am J Physiol. 2003; 284: G798-G807Google Scholar It may, therefore, be anticipated that a putatively slower release of free fatty acids (FFAs) from TGs during intestinal lipolysis may result in diminished responses from those that might occur in response to FFAs. Whether the effects of FFA on GE, secretion of CCK and PYY, which contribute to the regulation of energy intake,13Batterham R.L. Cowley M.A. Small C.J. et al.Gut hormone PYY(3-36) physiologically inhibits food intake.Nature. 2002; 418: 650-654Crossref PubMed Scopus (1918) Google Scholar, 14Kissileff H.R. Pi-Sunyer F.X. Thornton J. et al.C-terminal octapeptide of cholecystokinin decreases food intake in man.Am J Clin Nutr. 1981; 34: 154-160PubMed Scopus (494) Google Scholar and appetite, are greater than those of TG has important implications for understanding the gastrointestinal regulation of body weight. In rats, intraduodenal infusion of oleic acid (total load, 7.7 kcal) has been reported to suppress food intake by approximately 28% more than isocaloric infusion of triolein.15Woltman T. Castellanos D. Reidelberger R. Role of cholecystokinin in the anorexia produced by duodenal delivery of oleic acid in rats.Am J Physiol. 1995; 269: R1420-R1433PubMed Google Scholar However, because laboratory rats have a habitually low dietary fat intake and show low levels of pancreatic lipase and CCK secretion in response to intraduodenal TG,16Spannagel A.W. Nakano I. Tawil T. et al.Adaptation to fat markedly increases pancreatic secretory response to intraduodenal fat in rats.Am J Physiol. 1996; 270: G128-G135PubMed Google Scholar it is unclear whether these observations can be extrapolated to human beings. In human beings, Schwizer et al8Schwizer W. Asal K. Kreiss C. et al.Role of lipase in the regulation of upper gastrointestinal function in humans.Am J Physiol. 1997; 273: G612-G620PubMed Google Scholar reported that plasma CCK responses to FFA were greater than to TG, but failed to observe any differences in GE, probably because they did not specifically evaluate the fat component of the meal. Furthermore, although peak plasma CCK concentrations were approximately 7 pmol/L during intraduodenal infusion of a long-chain TG, they reached approximately 12 pmol/L during infusion of lauric acid, an FFA with 12 carbon atoms; and although energy intake was suppressed by approximately 900 kJ after TG (energy delivered, 1400 kJ),11Feinle C. O'Donovan D.G. Doran S. et al.Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.Am J Physiol. 2003; 284: G798-G807Google Scholar an equivalent reduction of energy intake was observed after infusion of only 10% as many kilojoules of lauric acid (energy delivered, 140 kJ).17Little T.J. Feltrin K.L. Horowitz M. et al.Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men.Am J Physiol. 2005; 289: R1090-R1098Google Scholar Thus, there is indirect evidence that the effects of FFA on gastrointestinal hormone secretion and energy intake in human beings are more potent than those of TG. We have evaluated the hypothesis that emulsified FFA would empty from the stomach more slowly, stimulate CCK and PYY secretion, and suppress appetite and energy intake more potently than TG. Oleic acid was compared with macadamia oil (∼84% monounsaturated FFA, predominantly oleic acid). A low-calorie protein control was used to determine that protein in the emulsions did not slow GE markedly. Nine men (age, 23.2 ± 1.8 y; range, 21–26 y; body mass index, 22.1 ± 0.7 kg/m2) were studied. We calculated that with 9 subjects we would observe a 10% difference in the primary end point, GE, between FFA and TG at an α value of 0.05, with a power of 0.98. Subjects were unrestrained eaters (scoring <12 on the eating restraint section [Factor 1] of the Three Factor Eating Questionnaire18Stunkard A.J. Messick S. The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger.J Psychosom Res. 1985; 29: 71-83Abstract Full Text PDF PubMed Scopus (3795) Google Scholar), had no gastrointestinal diseases or symptoms, were not taking medication known to affect gastrointestinal function or appetite, and did not consume more than 20 g of alcohol or more than 10 cigarettes/day. The study protocol was approved by the Royal Adelaide Hospital Research Ethics Committee. All subjects provided informed written consent. Subjects were studied on 3 occasions, separated by 3–10 days, in a single-blind, randomized fashion to evaluate the effects of intragastric administration of the following: (1) 40 g of oleic acid (FFA, Sigma Aldrich, Milwaukee, WI; 1830 kJ), (2) 40 g of macadamia oil (TG, Melrose Laboratories Pty Ltd., Victoria, Australia; 1856 kJ), both as 600-mL oil-in-water emulsions stabilized with 4% (wt/vol) powdered milk protein (Fonterra Brand Pty Ltd., Victoria, Australia), or (3) 600-mL aqueous solution of 4% powdered milk protein (control, 24 g milk protein in 600 mL water; 352 kJ), on GE, plasma CCK and PYY concentrations, appetite, and energy intake. Subjects were informed that the aim of the study was to evaluate GE of meals of varying nutrient composition. Subjects attended the Department of Nuclear Medicine, Positron Emission Tomography and Bone Densitometry at the Royal Adelaide Hospital at either 8:30 am or 10:30 am after an overnight fast from both solids and liquids from 10:00 pm onward. The reason for different start times was logistical. Subjects ingested a 120-mg potassium iodide capsule to block the thyroid from the uptake of radioactive iodine and then were intubated with a nasogastric feeding tube. The study protocol is outlined in Figure 1. After collection of a baseline blood sample and visual analogue scale (VAS) questionnaire to assess appetite perceptions (t = −10 min), the test emulsion/solution was instilled into the stomach over 5 minutes (t = −5 to 0 min). In study conditions (i) and (ii), the emulsions containing FFA or TG were labeled with 15 MBq of gamma-emitting 123I. The labeling was achieved by conjugating elemental 123I to 0.5 g of oleic acid or macadamia oil, as described.19Meyer J.H. Hlinka M. Kao D. et al.Gastric emptying of oil from solid and liquid meals Effect of human pancreatic insufficiency.Dig Dis Sci. 1996; 41: 1691-1699Crossref PubMed Scopus (42) Google Scholar, 20Meyer J.H. Elashoff J.D. Domeck M. et al.Control of canine gastric emptying of fat by lipolytic products.Am J Physiol. 1994; 266: G1017-G1035PubMed Google Scholar, 21Meyer J.H. Elashoff J.D. Lake R. Gastric emptying of indigestible versus digestible oils and solid fats in normal humans.Dig Dis Sci. 1999; 44: 1076-1082Crossref PubMed Scopus (24) Google Scholar In study condition (iii), the protein solution was labeled with 15 MBq of 99mTc–sulfur colloid. The aqueous phase of the fat-containing meals was not labeled with a radioactive tracer because of limitations in the radiation exposure permitted for volunteers. After instillation of the meal the nasogastric tube was removed and GE was measured for 240 minutes. Blood samples were collected at t = 0, 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes, and the VAS was completed at t = 0, 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 210, and 240 minutes. At t = 240 minutes, subjects were presented with a cold, buffet-style meal and invited to eat freely until they were comfortably full, for up to 30 minutes.22Feltrin K.L. Little T.J. Meyer J.H. et al.Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length.Am J Physiol. 2004; 287: R524-R533Google Scholar Immediately after the meal (ie, at t = 270 min), a final blood sample was collected and a VAS was completed. No blood samples were taken during the buffet meal period to avoid distraction of the subjects during eating. GE was measured scintigraphically by obtaining 1-minute anterior and 1-minute posterior images, with the subject standing, at t = 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, and 240 minutes. Data were corrected for subject movement and radionuclide decay, as described.23Collins P.J. Horowitz M. Cook D.J. et al.Gastric emptying in normal subjects—a reproducible technique using a single scintillation camera and computer system.Gut. 1983; 24: 1117-1125Crossref PubMed Scopus (391) Google Scholar Correction for tissue attenuation was performed by obtaining geometric mean counts. The lag phase (the last frame before radionuclide activity was detectable in the small intestine) was determined. To evaluate intragastric meal distribution, the total stomach region-of-interest was divided into proximal (fundus and proximal corpus) and distal (corpus and antrum) regions.24Horowitz M. Jones K. Edelbroek M.A. et al.The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite.Gastroenterology. 1993; 105: 382-390Abstract PubMed Google Scholar GE curves were constructed to derive the percentage retention in the total, proximal, and distal stomach.25Jones K.L. Tonkin A. Horowitz M. et al.Rate of gastric emptying is a determinant of postprandial hypotension in non-insulin-dependent diabetes mellitus.Clin Sci (Lond). 1998; 94: 65-70PubMed Google Scholar Venous blood samples (10 mL) were collected into ice-chilled ethylenediaminetetraacetic acid–treated tubes containing 400 kIU aprotinin per milliliter of blood (Trasylol; Bayer Australia Ltd, Pymble, Australia). Plasma was separated by centrifugation at 3200 rpm for 15 minutes at 4°C within 30 minutes of collection, and stored at −70°C until assayed. Plasma CCK concentrations (pmol/L) were determined using an established radioimmunoassay.26MacIntosh C.G. Morley J.E. Wishart J. et al.Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging.J Clin Endocrinol Metab. 2001; 86: 5830-5837Crossref PubMed Scopus (152) Google Scholar The intra-assay coefficient of variation was 9% and the interassay coefficient of variation was 27%. The assay has a sensitivity of 2.5 pmol/L.26MacIntosh C.G. Morley J.E. Wishart J. et al.Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging.J Clin Endocrinol Metab. 2001; 86: 5830-5837Crossref PubMed Scopus (152) Google Scholar Plasma PYY concentrations (pmol/L) were measured using an established radioimmunoassay.27Pilichiewicz A.N. Little T.J. Brennan I.M. et al.Effects of load, and duration, of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men.Am J Physiol. 2006; 290: R668-R677Google Scholar The assay has a sensitivity of 1.5 pmol/L; the interassay coefficient of variation was 16.6% and the intra-assay coefficient of variation was 12.3%.27Pilichiewicz A.N. Little T.J. Brennan I.M. et al.Effects of load, and duration, of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men.Am J Physiol. 2006; 290: R668-R677Google Scholar Hunger and fullness were measured using a validated VAS.28Parker B. Sturm K. MacIntosh C.G. et al.Relation between food intake and visual analogue rating scales of appetite and other sensations in healthy older and young subjects.Eur J Clin Nutr. 2004; 58: 212-218Crossref PubMed Scopus (241) Google Scholar Nausea and bloating also were assessed. Each VAS evaluated a sensation on a 100-mm horizontal line, where 0 mm represented sensation not felt at all and 100 mm represented sensation felt the greatest. Subjects indicated how they were feeling at that particular time by placing a vertical mark on the line. At the buffet meal, energy intake (kJ) was analyzed using commercially available software (Foodworks 3.01; Xyris Software, Highgate Hill, Queensland, Australia).22Feltrin K.L. Little T.J. Meyer J.H. et al.Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length.Am J Physiol. 2004; 287: R524-R533Google Scholar For VAS scores and plasma CCK and PYY concentrations, baseline values (0) were calculated as the means of values obtained at t = −10 and t = 0 minutes, and data were expressed as changes from baseline. The amount of fatty acid emptied (g) (for the TG this was calculated by subtracting the weight of glycerol); the percentage retention in the total, proximal, and distal stomach; and VAS data were analyzed by repeated-measures analysis of variance (ANOVA) with time and treatment as factors. Post hoc paired comparisons, corrected for multiple comparisons using Bonferroni's correction, were performed if ANOVAs revealed significant effects. For energy intake, the a priori hypothesis (ie, that the effect of FFA on energy intake was greater than that of TG), was evaluated by performing planned comparisons using the Student t test. Statistical significance was accepted at a P value of less than .05. Data are presented as means ± SEM. The study protocol was well tolerated. Intragastric administration of the meals was not associated with gastrointestinal symptoms or other adverse effects. Emptying of the control solution approximated an overall mono-exponential fashion, whereas the FFA and TG emulsions emptied much slower in an overall linear fashion, after an initial lag phase of 13 ± 2 minutes for TG, and of 46 ± 8 minutes for FFA. There was a treatment by time interaction for the amount of FFA and TG remaining in the total stomach (P < .001). Intragastric retention of FFA was greater than that of TG between t = 90 and t = 240 minutes (P < .001) (Figure 2A). The control solution emptied from the stomach completely within the 240 minutes (time effect, P < .001). When expressed as grams emptied, there was no significant difference in the amount of FFA and TG (FFA equivalent) emptied during the first 30 minutes (Figure 3), but between t = 45 and t = 240 minutes the amount of TG emptied was greater than that of FFA (P < .05). Emptying of TG occurred at a rate of approximately 0.9 kcal/min between 0 and 120 minutes, and at approximately 1.7 kcal/min between 120 and 240 minutes, whereas FFA emptied at a constant rate of approximately 0.2 kcal/min between 0 and 240 minutes.Figure 3Grams of fatty acid emptied after intragastric administration of (1) 40 g FFA or (2) 40 g TG, both as 600-mL oil-in-water emulsions, stabilized with 4% (wt/vol) powered milk protein. Data are means ± SEM (n = 9). #FFA vs TG: P < .05. ■, TG; ○, FFA.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Emptying of FFA and TG from the proximal stomach approximated the same pattern as for the total stomach. There was a treatment*time interaction for the amount remaining in the proximal stomach (P < .001) (Figure 2B). At t = 45 and between t = 120 and t = 240 minutes the amount of FFA in the proximal stomach was substantially greater than that of TG (P < .05 for all). There was a treatment*time interaction for the amount of fat remaining in the distal stomach (P < .01) (Figure 2C). At t = 150 and t = 180 minutes the amount of FFA in the distal stomach was greater when compared with TG, although the magnitude of this difference was modest. All treatments stimulated the release of CCK when compared with baseline, with peak values occurring at t = 10 minutes (time effect, P < .05) (Figure 4A). Plasma CCK values were greater than baseline between t = 0 and t = 90 minutes for control, between t = 0 and t = 20 minutes for TG, and between t = 0 and t = 240 minutes for FFA (P < .05 for all). There was a treatment*time interaction for plasma CCK (P < .001). Plasma CCK was greater in response to FFA, when compared with TG between t = 0 and t = 240 minutes (P < .05) and with control between t = 0 and t = 45 minutes and t = 90 and t = 240 minutes (P < .05). After the initial increase in plasma CCK values in response to all meals, concentrations subsequently decreased until approximately t = 45 minutes, despite a linear, or increasing, rate of GE. At t = 45 and t = 60 minutes, plasma CCK values were greater for controls when compared with TG (P < .05). At t = 240 minutes (ie, immediately before the meal), plasma CCK values still were above baseline for FFA, but not for control and TG. After the buffet meal (t = 270 min), plasma CCK values increased after all treatments, with no difference in the magnitude of the increase. The plasma CCK value after meal ingestion was comparable with peak concentrations in response to FFA. All treatments stimulated the release of PYY when compared with baseline (P < .001) (Figure 4B). Plasma PYY was greater than baseline between t = 10 and t = 90 minutes for control, between t = 20 and t = 90 minutes for TG, and between t = 10 and t = 240 minutes for FFA (P < .05, for all). There was a treatment by time interaction for plasma PYY (P < .001). Plasma PYY was greater in response to FFA when compared with TG between t = 20 and t = 45 minutes and between t = 90 and t = 240 minutes (P < .05), and with control between t = 10 and t = 240 minutes (P < .05). At t = 60 minutes and between t = 180 and t = 240 minutes, plasma PYY values were greater for TG when compared with control (P < .05). At t = 240 minutes (ie, immediately before the meal), PYY values still were above baseline for FFA and TG, but not for control. After the buffet meal (t = 270 min), the plasma PYY value increased after all treatments, with no difference in the magnitude of the increase. There was a treatment*time interaction for hunger (P < .001) and fullness (P < .05) scores (Figures 5A and B). Hunger decreased compared with baseline after ingestion of FFA (P < .001), and only returned to baseline at approximately 120 minutes. In contrast, after both control and TG, hunger increased steadily throughout the study period. Hunger was less in response to FFA when compared with control between t = 10 and t = 150 minutes (P < .05), and TG between t = 10 and t = 240 minutes, and greater in response to TG when compared with control between t = 20 and t = 240 minutes (P < .05). Fullness increased from baseline immediately after all treatments (time effect, P < .001), and was greater in response to FFA compared with both TG and control between t = 10 and t = 240 minutes (P < .01), with no difference between TG and control. At t = 240 minutes, hunger did not differ between control and FFA, but was greater with TG compared with control; fullness was greater with FFA compared with TG and control. There was substantial interindividual variability in energy intake from the buffet meal (Table 1). However, the mean energy intake after FFA was approximately 555 kJ less when compared with control, and approximately 1265 kJ less when compared with TG, the latter difference being close to statistically significant (P = .08). In contrast, energy intake after TG was greater by approximately 710 kJ when compared with control.Table 1Energy Intake (kJ) at the Buffet MealComparisonAverage (kJ)SD95% Confidence intervalTG-control+7091587−511 to 1929FFA-control−5551446−1667 to 556FFA-TG−12641945−2759 to 230NOTE. Measurements taken 240 minutes after intragastric administration of (1) 40 g FFA, (2) 40 g TG, both as 600-mL oil-in-water emulsions, stabilized with 4% (wt/vol) powered milk protein, or (3) control solution (24 g skim milk powder in 600 mL water). Data are means ± SD (n = 9). Open table in a new tab NOTE. Measurements taken 240 minutes after intragastric administration of (1) 40 g FFA, (2) 40 g TG, both as 600-mL oil-in-water emulsions, stabilized with 4% (wt/vol) powered milk protein, or (3) control solution (24 g skim milk powder in 600 mL water). Data are means ± SD (n = 9). Our observations indicate that the effects of FFA on CCK and PYY release and perceptions of fullness and hunger are substantially greater than those of TG. Furthermore, we observed a trend for FFA to reduce energy intake when compared with TG. These findings are consistent with previous studies in rats15Woltman T. Castellanos D. Reidelberger R. Role of cholecystokinin in the anorexia produced by duodenal delivery of oleic acid in rats.Am J Physiol. 1995; 269: R1420-R1433PubMed Google Scholar and pigs29Gregory P.C. Rayner D.V. The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.J Physiol. 1987; 385: 471-481PubMed Google Scholar and with indirect comparisons in human beings.11Feinle C. O'Donovan D.G. Doran S. et al.Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.Am J Physiol. 2003; 284: G798-G807Google Scholar, 17Little T.J. Feltrin K.L. Horowitz M. et al.Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men.Am J Physiol. 2005; 289: R1090-R1098Google Scholar FFAs also empty more slowly than TG8Schwizer W. Asal K. Kreiss C. et al.Role of lipase in the regulation of upper gastrointestinal function in humans.Am J Physiol. 1997; 273: G612-G620PubMed Google Scholar; over our 240-minute observation period, 26 g of TG vs 9.5 g of FFA emptied from the stomach. Despite the approximately 2.5-fold greater emptying of TG, plasma concentrations of CCK and PYY and perceptions of fullness were nearly twice as great in response to FFA, suggesting that FFAs are approximately 5 times more effective per gram than TG. We interpret these differences to mean that gastrointestinal and appetite responses are highly dependent on the FFA concentration in the gastrointestinal lumen, and that postprandial concentrations must have been considerably
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