scholarly journals Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects

2009 ◽  
Vol 296 (3) ◽  
pp. G482-G489 ◽  
Author(s):  
Feruze Yılmaz Enç ◽  
Tunç Öneş ◽  
H. Levent Akın ◽  
Fuat Dede ◽  
H. Turgut Turoğlu ◽  
...  

Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP ( r = 0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 ( r = −0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.

2001 ◽  
Vol 281 (3) ◽  
pp. G752-G763 ◽  
Author(s):  
Feruze Y. Enç ◽  
Neşe I˙meryüz ◽  
Levent Akin ◽  
Turgut Turoğlu ◽  
Fuat Dede ◽  
...  

We investigated the effect of acarbose, an α-glucosidase and pancreatic α-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 ( r = 0.68 , P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.


1997 ◽  
Vol 273 (2) ◽  
pp. G374-G380 ◽  
Author(s):  
J. Borovicka ◽  
W. Schwizer ◽  
C. Mettraux ◽  
C. Kreiss ◽  
B. Remy ◽  
...  

Gastric lipase (HGL) contributes significantly to fat digestion. However, little is known about its neurohormonal regulation in humans. We studied the role of CCK and cholinergic mechanisms in the postprandial regulation of HGL and pancreatic lipase (HPL) secretion in six healthy subjects. Gastric emptying of a mixed meal and outputs of HGL, pepsin, acid, and HPL were determined with a double-indicator technique. Three experiments were performed in random order: intravenous infusion of 1) placebo, 2) low-dose atropine (5 micrograms.kg-.h-1), and 3) the CCK-A receptor antagonist loxiglumide (22 mumol.kg-.h-1). Atropine decreased postprandial outputs of HGL, pepsin, gastric acid, and HPL (P < 0.03) while slowing gastric emptying (P < 0.05). Loxiglumide markedly increased the secretion of HGL, pepsin, and acid while distinctly reducing HPL outputs and accelerating gastric emptying (P < 0.03). Plasma CCK and gastrin levels increased during loxiglumide infusion (P < 0.03). Atropine enhanced gastrin but not CCK release. Postprandial HGL, pepsin, and acid secretion are under positive cholinergic but negative CCK control, whereas HPL is stimulated by cholinergic and CCK mechanisms. We conclude that CCK and cholinergic mechanisms have an important role in the coordination of HGL and HPL secretion to optimize digestion of dietary lipids in humans.


2006 ◽  
Vol 96 (5) ◽  
pp. 883-887 ◽  
Author(s):  
Reawika Chaikomin ◽  
Antonietta Russo ◽  
Christopher K. Rayner ◽  
Christine Feinle-Bisset ◽  
Deirdre G. O'Donovan ◽  
...  

The rate of alcohol absorption is dependent on gastric emptying (GE). As the slowing of GE by fat is dependent on lipolysis, orlistat may increase the rise in blood alcohol when alcohol is consumed with, or after, fat. The aim of the study was to evaluate the effects of orlistat on GE and blood alcohol after an alcohol-containing drink following a fat ‘preload’, in healthy subjects. Ten healthy males consumed 120 ml cream with or without 120 mg orlistat, 30 min before an alcohol-containing drink labelled with 20 MBq [99 mTc]sulfur colloid on 2 d. GE, plasma alcohol and blood glucose were measured. GE was slightly faster with orlistat (P<0·05) compared with control. Plasma alcohol at 15 min was slightly higher with orlistat (0·034 (sem 0·006) g/100 ml) v. control (0·029 (sem 0·005) g/100 ml) (P<0·05), but there was no effect on the area under the curve 0–240 min. The increase in blood glucose was greater with orlistat, for example, at 15 min (1·07 (sem 0·2) mmol/l) v. control (0·75 (sem 0·2) mmol/l) (P=0·05). The rise in blood glucose and plasma alcohol were related (for example, at 15 min r 0·49; P=0·03). In conclusion, lipase inhibition accelerates GE of an alcohol-containing drink following a fat ‘preload’ with a minor increase in the initial rise in plasma alcohol.


Author(s):  
Grant Greaves ◽  
Richard Xiang ◽  
Hossein Rafiei ◽  
Adeeb Malas ◽  
Jonathan P. Little

The main objective of this study was to determine whether acute ingestion of a ketone monoester (KME) supplement impacted mixed meal tolerance test (MMTT) glucose area under the curve (AUC). Nineteen healthy young volunteers (10 males/9 females, 24.7 ± 4.9 years, BMI = 22.7 ± 2.4) participated in a double-blind, placebo-controlled crossover study. Following overnight fasting (≥10 h), participants consumed 0.45mL/kg of a KME supplement or taste-matched placebo followed by a MMTT 15 minutes later. Blood samples were collected every 15-30 minutes over 2.5 hours. KME supplementation acutely raised beta-hydroxybutyrate (β-OHB) AUC (590%, P < 0.0001, d = 2.4) and resulted in decreases in blood glucose AUC (-9.4%, P = 0.03, d = 0.56) and non-esterified fatty acid (NEFA) AUC (-27.3%, P = 0.023, d = 0.68) compared to placebo. No differences were found for plasma insulin AUC (P = 0.70) or gastric emptying estimated by co-ingested acetaminophen AUC (P = 0.96) between ketone and placebo. Overall, results indicate that KME supplementation attenuates postprandial glycemic and NEFA responses when taken 15 min prior to a mixed meal in young healthy individuals. Future studies are warranted to investigate whether KME supplementation may benefit individuals with impaired glycemic control. Novelty Bullets • Acute ketone monoester supplementation 15 min prior to a mixed meal decreased postprandial glucose and non-esterified fatty acid (NEFA) levels without significantly impacting postprandial insulin or estimates of gastric emptying. • Glucose and NEFA lowering effects of ketone monoester supplementation are apparently not mediated by changes in insulin release or gastric emptying.


2011 ◽  
Vol 107 (4) ◽  
pp. 601-613 ◽  
Author(s):  
Jill A. Parnell ◽  
Raylene A. Reimer

There is a growing interest in modulating gut microbiota with diet in the context of obesity. The purpose of the present study was to evaluate the dose-dependent effects of prebiotics (inulin and oligofructose) on gut satiety hormones, energy expenditure, gastric emptying and gut microbiota. Male lean and obese JCR:LA-cp rats were randomised to either of the following: lean 0 % fibre (LC), lean 10 % fibre (LF), lean 20 % fibre (LHF), obese 0 % fibre (OC), obese 10 % fibre (OF) or obese 20 % fibre (OHF). Body composition, gastric emptying, energy expenditure, plasma satiety hormone concentrations and gut microbiota (using quantitative PCR) were measured. Caecal proglucagon and peptide YY mRNA levels were up-regulated 2-fold in the LF, OF and OHF groups and 3-fold in the LHF group. GhrelinO-acyltransferase mRNA levels were higher in obesev.lean rats and decreased in the OHF group. Plasma ghrelin response was attenuated in the LHF group. Microbial species measured in the Bacteroidetes division decreased, whereas those in the Firmicutes increased in obesev.lean rats and improved with prebiotic intake.BifidobacteriumandLactobacillusincreased in the OHFv.OC group.Bacteroidesand total bacteria negatively correlated with percentage of body fat and body weight. Enterobacteriaceae increased in conjunction with glucose area under the curve (AUC) and glucagon-like peptide-1 AUC.Bacteroidesand total bacteria correlated positively with ghrelin AUC yet negatively with insulin AUC and energy intake (P < 0·05). Several of the mechanisms through which prebiotics act (food intake, satiety hormones and alterations in gut microbiota) are regulated in a dose-dependent manner. The combined effects of prebiotics may have therapeutic potential for obesity.


2005 ◽  
Vol 289 (3) ◽  
pp. E504-E507 ◽  
Author(s):  
Reawika Chaikomin ◽  
Selena Doran ◽  
Karen L. Jones ◽  
Christine Feinle-Bisset ◽  
Deirdre O'Donovan ◽  
...  

The rate of gastric emptying of glucose-containing liquids is a major determinant of postprandial glycemia. The latter is also dependent on stimulation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Although overall emptying of glucose approximates 1–3 kcal/min, the “early phase” of gastric emptying is usually more rapid. We have evaluated the hypothesis that increased stimulation of incretin hormones and insulin by a more rapid initial rate of small intestinal glucose delivery would reduce the overall glycemic response to a standardized enteral glucose load. Twelve healthy subjects were studied on two separate days in which they received an intraduodenal (id) glucose infusion for 120 min. On one day, the infusion rate was variable, being more rapid (6 kcal/min) between t = 0 and 10 min and slower (0.55 kcal/min) between t = 10 and 120 min, whereas on the other day the rate was constant (1 kcal/min) from t = 0–120 min, i.e., on both days 120 kcal were given. Between t = 0 and 75 min, plasma insulin, GIP, and GLP-1 were higher with the variable infusion. Despite the increase in insulin and incretin hormones, blood glucose levels were also higher. Between t = 75 and 180 min, blood glucose and plasma insulin were lower with the variable infusion. There was no difference in the area under the curve 0–180 min for blood glucose. We conclude that stimulation of incretin hormone and insulin release by a more rapid initial rate of id glucose delivery does not lead to an overall reduction in glycemia in healthy subjects.


2012 ◽  
Vol 112 (4) ◽  
pp. 552-559 ◽  
Author(s):  
Lucy K. Wasse ◽  
Caroline Sunderland ◽  
James A. King ◽  
Rachel L. Batterham ◽  
David J. Stensel

The reason for high altitude anorexia is unclear but could involve alterations in the appetite hormones ghrelin and peptide YY (PYY). This study examined the effect of resting and exercising in hypoxia (12.7% O2; ∼4,000 m) on appetite, energy intake, and plasma concentrations of acylated ghrelin and PYY. Ten healthy males completed four, 7-h trials in an environmental chamber in a random order. The four trials were control-normoxia, control-hypoxia, exercise-normoxia, and exercise-hypoxia. During exercise trials, participants ran for 60 min at 70% of altitude-specific maximal oxygen consumption (V̇o2max) and then rested. Participants rested throughout control trials. A standardized meal was consumed at 2 h and an ad libitum buffet meal at 5.5 h. Area under the curve values for hunger (assessed using visual analog scales) tended to be lower during hypoxic trials than normoxic trials (repeated-measures ANOVA, P = 0.07). Ad libitum energy intake was lower ( P = 0.001) in hypoxia (5,291 ± 2,189 kJ) than normoxia (7,718 ± 2,356 kJ; means ± SD). Mean plasma acylated ghrelin concentrations were lower in hypoxia than normoxia (82 ± 66 vs. 100 ± 69 pg/ml; P = 0.005) while PYY concentrations tended to be higher in normoxia (32 ± 4 vs. 30 ± 3 pmol/l; P = 0.059). Exercise suppressed hunger and acylated ghrelin and increased PYY but did not influence ad libitum energy intake. These findings confirm that hypoxia suppresses hunger and food intake. Further research is required to determine if decreased concentrations of acylated ghrelin orchestrate this suppression.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1739 ◽  
Author(s):  
Zhuoshi Zhang ◽  
Bernard Venn ◽  
John Monro ◽  
Suman Mishra

The satiating capacity of carbohydrate staples eaten alone is dependent upon the energy density of the food but relative satiety when starchy staples are incorporated into mixed meals is uncertain. Our aim was to assess the satiating effects of three carbohydrate staples; jasmine rice, penne pasta, and Agria potato, each consumed within a standard mixed meal. Cooked portions of each staple containing 45 g carbohydrate were combined with 200 g of meat sauce and 200 g of mixed vegetables in three mixed meals. The quantities of staple providing 45 g carbohydrate were: Rice, 142 g; pasta, 138 g and potato 337 g. Participants (n = 14) consumed each of the mixed meals in random order on separate days. Satiety was assessed with using visual analogue scales at baseline and for 3 h post meal. In an area-under-the-curve comparison, participants felt less hungry (mean (SD)) following potato 263 (230) than following rice 374 (237) or pasta 444 (254) mm∙min, and felt fuller, more satisfied, and wanted to eat less following the potato compared with the rice and pasta meals (p for all <0.01). The superior satiating effect of potato compared with rice and pasta in a mixed meal was consistent with its lower energy density.


2016 ◽  
Vol 26 (5) ◽  
pp. 435-444
Author(s):  
James R. Rowe ◽  
Kyle D. Biggerstaff ◽  
Vic Ben-Ezra ◽  
David L. Nichols ◽  
Nancy DiMarco

This study examined the effect of prior exercise on postprandial lipemia (PPL) concentration following a mixed meal (MM) made with either glucose or fructose. Sedentary women completed four trials in random order: 1) Rest-Fructose: RF, 2) Rest-Glucose: RG, 3) Exercise-Fructose: EF, 4) Exercise-Glucose: EG. Exercise expended 500 kcal while walking at 70%VO2max. Rest was 60 min of sitting. The morning after each trial, a fasting (12 hr) blood sample was collected followed by consumption of the MM. The MM was blended with whole milk and ice cream plus a glucose or fructose powder. Glucose and fructose powder accounted for 30% of the total kcal within the MM. Blood was collected periodically for 6 hr post-MM and analyzed for PPL. Magnitude of PPL over the 6 hr postmeal was quantified using the triglyceride incremental area under the curve (TG AUCI). Significant differences (p < .05) between trials were determined using repeated-measures ANOVA and Bonferroni post hoc test. There was no significant difference in the TG AUCI between the four trials (p > .05). A significant trial by time interaction for TG concentration was reported (p < .05). Despite lack of change in the AUCI with prior exercise, the lower TG concentration at multiple time points in the EG trial does indicate that prior exercise has some desirable effect on PPL. This study suggests that replacing fructose with glucose sugars and incorporating exercise may minimize PPL following a mixed meal but exercise will need to elicit greater energy expenditure.


2019 ◽  
Vol 20 (7) ◽  
pp. 750-758 ◽  
Author(s):  
Yi Wu ◽  
Hengxun He ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.


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