Postprandial Satiety Research Articles

Leptin and cholecystokinin in Schizothorax prenanti: Molecular cloning, tissue expression, and mRNA expression responses to periprandial changes and fasting

In the present study, full-length cDNA sequences of leptin and cholecystokinin (CCK) were cloned from Schizothorax prenanti (S. prenanti), and applied real-time quantitative PCR to characterize the tissue distribution, and appetite regulatory effects of leptin and CCK in S. prenanti. The S. prenanti leptin and CCK full-length cDNA sequences were 1121bp and 776bp in length, encoding the peptide of 171 and 123 amino acid residues, respectively. Tissue distribution analysis showed that leptin mRNA was mainly expressed in the liver of S. prenanti. CCK was widely expressed, with the highest levels of expression in the hypothalamus, myelencephalon, telencephalon and foregut of S. prenanti. The CCK mRNA expression was highly elevated after feeding, whereas the leptin mRNA expression was not affected by single meal. These results suggested that CCK is a postprandial satiety signal in S. prenanti, but leptin might not be. In present study, leptin and CCK gene expression were both decreased after fasting and increased after refeeding, which suggested leptin and CCK might be involved in regulation of appetite in S. prenanti. This study provides an essential groundwork to further elucidate the appetite regulatory systems of leptin and CCK in S. prenanti as well as in other teleosts.

Dietary pulses, satiety and food intake: a systematic review and meta-analysis of acute feeding trials.

To assess the effect of dietary pulses (beans, peas, chickpeas, lentils) on acute satiety and second meal intake, a systematic review and meta-analysis was conducted. MEDLINE, EMBASE, CINAHL, and the Cochrane Registry (through May 6, 2013) were searched for acute controlled trials examining the effect of dietary pulses on postprandial satiety or second meal intake compared with isocaloric controls. Two independent reviewers extracted data and assessed methodological quality and risk of bias. Data were pooled by generic inverse variance random effects models and expressed as ratio of means (RoMs) for satiety and mean differences (MDs) for second meal food intake, with 95% confidence intervals (95% CIs). Heterogeneity was assessed (Q statistic) and quantified (I(2) statistic). Protocol registration: clinicaltrials.gov identifier, NCT01605422. Nine trials met the eligibility criteria. Dietary pulses produced a 31% greater satiety incremental area under the curve (IAUC) (RoM = 1.31, 95% CI: 1.09 to 1.58, P = 0.004; Phet = 0.96; I(2) = 0%) without affecting second meal intake (MD = -19.94, 95% CI: -75-35, P = 0.48; Phet = 0.01; I(2) = 63%). Our data are limited by the small sample sizes, narrow participant characteristics and significant unexplained heterogeneity among the available trials. Pooled analyses show that dietary pulses contribute to acute satiety but not second meal intake.

The effect of eating rate on satiety in healthy and overweight people – A pilot study

Background & aims: Eating rate has gained the attention of scientific research due to its potential association with obesity and its co-morbidities, though evidence of its effects on satiety is limited. This study aimed to assess if eating rate affects postprandial satiety, in seven healthy and seven overweight/obese subjects. Methods: Participants were randomised to a 2-way crossover study of two controlled eating rates. Following anthropometric measurements, isocaloric meals were consumed at a slow and fast eating rate. Perceived satiety was measured at regular intervals using visual analogue scales. Results: The overweight group consumed the fast eating rate meal significantly faster (5±0.8min) than the healthy weight group (8.3±0.4min, p=0.004). Total area under curve from visual analogue scale showed a trend towards lower perceived fullness after the fast eating rate compared to slow rate (p=0.08) in all participants. Significant correlations were observed between eating time and body mass index (p=0.005), visceral fat score (p=0.0003) and trunk fat percentage (p=0.023) on the fast-rate protocol. Conclusions: The overweight fast eating rate group consumed the meal at a faster eating rate than the healthy weight fast eating rate group and the trend towards reduced perceived fullness when eating at a fast eating rate may, in part, contribute to increased food intake in overweight individuals. The correlations between eating time and body composition suggest faster eating rate is associated with a greater risk of higher BMI, visceral fat score and trunk fat percentage, making this the first laboratory study to make these observations. © 2014 European Society for Clinical Nutrition and Metabolism.

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

Melanocortin 4 receptor (MC4R) has a major role in energy homeostasis. The rs17782313 polymorphism, mapped 188kb downstream from MC4R, has been associated with satiety, higher body mass index (BMI) and total calorie intake in adults. To assess the association of rs17782313 with gastric functions, satiation, or satiety, we studied 178 predominantly Caucasian overweight and obese people: 120 females, 58 males; mean BMI 33.4±5.3kg/m(2) (SD); age 37.7±11.2years. Quantitative traits assessed were gastric emptying (GE) of solids and liquids; fasting and postprandial gastric volume; satiation by maximum tolerated volume and 4 symptoms by 100-mm visual analog scales (VAS); and satiety by ad libitum buffet meal. Associations of genotype and quantitative traits were assessed by analysis of covariance (using gender and BMI as covariates), based on a dominant [TC (n=72)-CC (n=12) vs. TT (n=94)] genetic model. rs17782313(C) was associated with postprandial satiation symptoms (median Δ total VAS 26.5mm, p=0.036), reduced proportion of solid GE at 2h (median Δ 6.7%, p=0.008) and 4h (median Δ 3.2%, p=0.006), and longer t ½ (median Δ 6min, p=0.034). Associations of rs17782313 with obesity may be explained by reduced satiation and GE. The role of MC4R mechanisms in satiation and gastric function deserves further study.

Enrichment of biscuits and juice with oat β-glucan enhances postprandial satiety

Effects of fibre and β-glucan on satiety have been reported in many studies, but no consensus has been reached. The aim of this study was to examine the effects of breakfasts varying in the dose of oat bran (4g or 8g β-glucan). The approach was to study whether the food matrix (solid or liquid) into which the oat bran is incorporated influences postprandial satiety in otherwise similar meal settings. Thirty healthy females were offered four different breakfasts: biscuits+juice (0g β-glucan), enriched biscuits+juice (4g β-glucan), biscuits+enriched juice (4g β-glucan) and enriched biscuits+enriched juice (8g β-glucan) in a random order on separate test days. The sensations associated with hunger and satiety were evaluated using visual analogue scales (VAS) before and after ingesting the test breakfasts and every 30min until 210min. Oat bran addition in breakfasts increased postprandial satiety especially when both juice and biscuits were enriched (8g of β-glucan). Addition of oat bran to juice enhanced satiety and related feelings more effectively than the addition into biscuits.

Protein PYY and its role in metabolism.

The hormone PYY is released from the distal gut in response to nutrient ingestion. Numerous studies have shown that PYY3-36, the most abundant circulating isoform of PYY, reduces food intake when given to obese rodents and humans. Its infusion to mimic postprandial levels in fasting subjects inhibits appetite, suggesting a physiological role in postprandial satiety. However, the mechanisms underlying this effect remain unclear. Neuronal activity within several brain areas appears to be modified following peripheral administration of PYY3-36 and a direct effect on the central nervous system is possible. Several studies suggest that PYY3-36 levels are reduced in obesity and are elevated following gastric bypass surgery, possibly contributing to the increased feelings of satiety following this procedure. Whether PYY has a role in the regulation of energy expenditure is currently unclear. However, due to the clear appetite-inhibitory effect of PYY, this hormone continues to be investigated as a potential therapeutic agent in the treatment of obesity.

Identification of Sphingolipid Metabolites That Induce Obesity via Misregulation of Appetite, Caloric Intake and Fat Storage in Drosophila

Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Drosophila genetic manipulations to cause accumulation or depletion of ceramide and sphingosine-1-phosphate (S1P) intermediates. Sphingolipidomic profiles were characterized across mutants for various sphingolipid metabolic genes using liquid chromatography electrospray ionization tandem mass spectroscopy. Biochemical assays and microscopy were used to assess classic hallmarks of obesity including elevated fat stores, increased body weight, resistance to starvation induced death, increased adiposity, and fat cell hypertrophy. Multiple behavioral assays were used to assess appetite, caloric intake, meal size and meal frequency. Additionally, we utilized DNA microarrays to profile differential gene expression between these flies, which mapped to changes in lipid metabolic pathways. Our results show that accumulation of ceramides is sufficient to induce obesity phenotypes by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) Modulating the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr, resulting in caloric intake-dependent obesity.

Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults

Introduction:Mechanisms for liraglutide-induced weight loss are poorly understood.Objective:We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals.Design:Participants (N=49, 18–75 years, body mass index: 30–40 kg m−2) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed.Results:Five-hour gastric emptying (AUC0–300 min) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80–1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5–0.6 mmol l−1 versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC0–300 min (by ∼26% versus placebo, P=0.02). Glucagon iAUC0–300 min decreased by ∼30%, and iAUC0–60 min for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. Funding: Novo Nordisk.Conclusion:Gastric emptying AUC0–300 min was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

Impaired postprandial fullness in Type 2 diabetic subjects is rescued by acute exercise independently of total and acylated ghrelin

Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM (N = 8) and healthy controls (N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could be eaten, nausea, and fullness) and circulating levels of glucose, insulin, and total and acylated ghrelin were measured at baseline and in response to a 75 g oral glucose load, provided immediately after an aerobic exercise bout (1 h at 50% Wmax) or no exercise (rest trial), on two separate occasions. Baseline levels of total (284.4 ± 15.9 and 397.6 ± 35.2 pmol/l) and acylated ghrelin (7.9 ± 1.0 and 13.7 ± 1.2 pmol/l) were lower in subjects with T2DM compared with healthy subjects (P < 0.05). In the rest trial, post- vs. preprandial feeling of fullness increased in healthy subjects but decreased in subjects with T2DM (healthy vs. T2DM; P < 0.05). Exercise increased postprandial fullness in the T2DM group (P < 0.05), while plasma ghrelin levels were unaffected. Our data suggest that the presence of T2DM likely drives suppressed ghrelin levels and poor appetite regulation, but a single exercise bout is sufficient to restore oral glucose-induced fullness independently of ghrelin.

The Impact of Food Viscosity on Eating Rate, Subjective Appetite, Glycemic Response and Gastric Emptying Rate

Understanding the impact of rheological properties of food on postprandial appetite and glycemic response helps to design novel functional products. It has been shown that solid foods have a stronger satiating effect than their liquid equivalent. However, whether a subtle change in viscosity of a semi-solid food would have a similar effect on appetite is unknown. Fifteen healthy males participated in the randomized cross-over study. Each participant consumed a 1690 kJ portion of a standard viscosity (SV) and a high viscosity (HV) semi-solid meal with 1000 mg acetaminophen in two separate sessions. At regular intervals during the three hours following the meal, subjective appetite ratings were measured and blood samples collected. The plasma samples were assayed for insulin, glucose-dependent insulinotropic peptide (GIP), glucose and acetaminophen. After three hours, the participants were provided with an ad libitum pasta meal. Compared with the SV meal, HV was consumed at a slower eating rate (P = 0.020), with postprandial hunger and desire to eat being lower (P = 0.019 and P<0.001 respectively) while fullness was higher (P<0.001). In addition, consuming the HV resulted in lower plasma concentration of GIP (P<0.001), higher plasma concentration of glucose (P<0.001) and delayed gastric emptying as revealed by the acetaminophen absorption test (P<0.001). However, there was no effect of food viscosity on insulin or food intake at the subsequent meal. In conclusion, increasing the viscosity of a semi-solid food modulates glycemic response and suppresses postprandial satiety, although the effect may be short-lived. A slower eating rate and a delayed gastric emptying rate can partly explain for the stronger satiating properties of high viscous semi-solid foods.

Growth hormone treatment modulates active ghrelin levels in rats

Introduction: Impairments in neuroendocrine regulation of food intake and postprandial satiety are leading causes to obesity. Ghrelin peptide is a GI hormone known to increase food intake partly through induction of growth hormone. The regulation of ghrelin production is still unknown. Objective: The aim of the current study is to investigate the influence of growth hormone (Genotropin) treatment on active ghrelin levels in plasma, stomach, pancreas and kidney in rats. Material/methods: Male Sprague-Dawley rats, randomly allocated into control and three treatment groups, received daily subcutaneous injections of Genotropin at 2, 20 and 100 µg/rat/day for 5 consecutive days. Active ghrelin levels were quantified per tissue mass or tissue protein. Results: In control groups, the highest active ghrelin concentration in pmol/g tissue was found in the stomach (15.5 ± 0.21) followed by the pancreas (1.96 ± 0.066) and the kidney (1.36 ± 0.037). Genotropin treatment caused a dose dependent decrease in active ghrelin concentration in stomach, kidney and pancreas with a concomitant increase in plasma, and reaching significance at 20 and 100 µg/rat/day doses. However, the treatment caused variable effect on total protein concentrations, with a decrease in pancreas and an increase in stomach and kidney supernatants. Consequently, under such treatment, determination of active ghrelin concentration per tissue mass rather than per tissue protein is favored. Conclusions: The present study suggests a direct correlation between Genotropin treatment and active ghrelin secretion into the rat plasma via modulating its stores in stomach, kidney and pancreas.

Short-term aerobic exercise training increases postprandial pancreatic polypeptide but not peptide YY concentrations in obese individuals

ObjectiveShort-term exercise training improves glycemic control, but the effect of short-term training on postprandial satiety peptide responses or perceived satiety remains unknown. We tested the hypothesis that short-term aerobic exercise training (15 days) would alter postprandial pancreatic and gut peptide [pancreatic polypeptide (PP) and peptide YY (PYY)] responses and perceived appetite and satiety in obese individuals.SubjectsThirteen healthy obese men and women (age: 42±2 y; BMI: 30-45 kg/m2)MeasurementsSubjects were studied before and after 15 days of training (walking 1 h at 70-75% VO2peak). On the study day, subjects consumed 1500 kcal as 6 meals (250 kcal: 9 g protein, 40 g CHO, 6 g fat) while blood samples and satiety measurements were taken at baseline and every 20 min for 12 h. Blood was analyzed for pancreatic polypeptide (PP), peptide YY (PYY), glucose, and insulin levels. Appetite and satiety was assessed with a visual analog scale throughout the day.ResultsIncremental area under the curve (iAUC) for PP increased significantly with training (pre 2788±753; post 3845±830 pg/ml·min for 12-h, p<0.001), but there was no difference in the PP response to each meal. The initial PP response to the first meal increased (ΔPPmin 20-0: pre 86±25; post 140±36 pg/ml, p<0.05) with training. PYY iAUC showed no significant changes with training but showed a significant main effect of time across meals, with the largest response being to the first meal (P<0.005). There were no changes in satiety, glucose, or insulin levels with training.ConclusionShort-term exercise training increases postprandial PP concentrations in obese individuals; however, PYY levels and glycemic control remain unaffected. Both PP and PYY show meal-induced increases at all meals but PYY has a greater response at the first meal with reduced responses at subsequent meals.

Increased Postprandial Energy Expenditure May Explain Superior Long Term Weight Loss after Roux-en-Y Gastric Bypass Compared to Vertical Banded Gastroplasty

Background and AimsGastric bypass results in greater weight loss than Vertical banded gastroplasty (VBG), but the underlying mechanisms remain unclear. In addition to effects on energy intake the two bariatric techniques may differentially influence energy expenditure (EE). Gastric bypass in rats increases postprandial EE enough to result in elevated EE over 24 hours. This study aimed to investigate alterations in postprandial EE after gastric bypass and VBG in humans.MethodsFourteen women from a randomized clinical trial between gastric bypass (n = 7) and VBG (n = 7) were included. Nine years postoperatively and at weight stability patients were assessed for body composition and calorie intake. EE was measured using indirect calorimetry in a respiratory chamber over 24 hours and focused on the periods surrounding meals and sleep. Blood samples were analysed for postprandial gut hormone responses.ResultsGroups did not differ regarding body composition or food intake either preoperatively or at study visit. Gastric bypass patients had higher EE postprandially (p = 0.018) and over 24 hours (p = 0.048) compared to VBG patients. Postprandial peptide YY (PYY) and glucagon like peptide 1 (GLP-1) levels were higher after gastric bypass (both p<0.001).ConclusionsGastric bypass patients have greater meal induced EE and total 24 hours EE compared to VBG patients when assessed 9 years postoperatively. Postprandial satiety gut hormone responses were exaggerated after gastric bypass compared to VBG. Long-term weight loss maintenance may require significant changes in several physiological mechanisms which will be important to understand if non-surgical approaches are to mimic the effects of bariatric surgery.

Liquid meal composition, postprandial satiety hormones, and perceived appetite and satiety in obese women during acute caloric restriction

The purpose of this study was to compare postprandial satiety regulating hormone responses (pancreatic polypeptide (PP) and peptide tyrosine tyrosine (PYY)) and visual analog scale- (VAS) assessed perceived appetite and satiety between liquid high-protein (HP) and high-carbohydrate (HC) meals in obese women during acute (24-h) caloric restriction. Eleven obese premenopausal women completed two conditions in random order in which they consumed 1500 calories as six 250-calorie HP meals or six 250-calorie HC meals over a 12-h period. Blood samples were taken at baseline and every 20 min thereafter and analyzed for PP and PYY concentrations. At these same points, perceived hunger and fullness were assessed with a VAS. The incremental area under the curve (iAUC) was used to compare postprandial responses. The 12-h PP and PYY iAUC were greater (P≤0.05) during the HP condition (PP: 4727±1306 pg/ml×12 h, PYY: 1373±357 pg/ml×12 h) compared with the HC condition (PP: 2300±528 pg/ml×12 h, PYY: 754±246 pg/ml×12 h). Perceived hunger and fullness were not different between conditions (P>0.05). The greatest changes in PYY and perceived fullness occurred after the morning meals during both conditions. These data suggest that in obese women during acute caloric restriction before weight loss, i) liquid HP meals, compared with HC meals, result in greater postprandial PP and PYY concentrations, an effect not associated with differential appetite or satiety responses, and ii) meal-induced changes in PYY and satiety are greatest during the morning period, regardless of dietary macronutrient composition.

The effect of eating rate on satiety in healthy and overweight people- a pilot study

Background & aims: Eating rate has gained the attention of scientific research due to its potential association with obesity and its co-morbidities, though evidence of its effects on satiety is limited. This study aimed to assess if eating rate affects postprandial satiety, in seven healthy and seven overweight/obese subjects. Methods: Participants were randomised to a 2-way crossover study of two controlled eating rates. Following anthropometric measurements, isocaloric meals were consumed at a slow and fast eating rate. Perceived satiety was measured at regular intervals using visual analogue scales. Results: The overweight group consumed the fast eating rate meal significantly faster (5±0.8min) than the healthy weight group (8.3±0.4min, p=0.004). Total area under curve from visual analogue scale showed a trend towards lower perceived fullness after the fast eating rate compared to slow rate (p=0.08) in all participants. Significant correlations were observed between eating time and body mass index (p=0.005), visceral fat score (p=0.0003) and trunk fat percentage (p=0.023) on the fast-rate protocol. Conclusions: The overweight fast eating rate group consumed the meal at a faster eating rate than the healthy weight fast eating rate group and the trend towards reduced perceived fullness when eating at a fast eating rate may, in part, contribute to increased food intake in overweight individuals. The correlations between eating time and body composition suggest faster eating rate is associated with a greater risk of higher BMI, visceral fat score and trunk fat percentage, making this the first laboratory study to make these observations. © 2014 European Society for Clinical Nutrition and Metabolism.

DIGESTIVE PHYSIOLOGY OF THE PIG SYMPOSIUM: G protein-coupled receptors in nutrient chemosensation and gastrointestinal hormone secretion1

The gastrointestinal tract is a highly effective and efficient organ system that digests and absorbs nutrients, contributes to the regulation of glucose homeostasis, and signals postprandial satiety. A network of enteroendocrine cells orchestrates these events through the release of neuropeptide hormones secreted in response to the specific nutrient components within the intraluminal milieu. Nutrient chemosensing by these cells is mediated by cell membrane proteins that have been localized to hormone-producing cells. However, functional studies of the nutrient detection abilities of the endocrine cell population have been limited due to its rare and singly distributed cell type. Recent technological advances have enabled investigations with primary endocrine cells that promise to enhance our current understanding of enteroendocrine cell biology. This review focuses on a particular subset of chemosensing receptors, the G protein-coupled receptors (GPCR), that have been identified as putative nutrient sensors of the major macronutrients, lipids, proteins, and carbohydrates by enteroendocrine cells. The contributions of these receptors in directly activating and stimulating hormone secretion in several subsets of enteroendocrine cells will be discussed, based on evidence gathered by functional studies in animal models, in vitro studies in endocrine cell lines, and newly described findings in primary endocrine cells. Key insights in chemosensory detection and hormone secretion from enteroendocrine cells may help further the studies in larger animal models and guide the formulation of feed or supplements to influence the gastrointestinal signals regulating optimal food intake, absorptive capacity, and growth.

Increasing the number of masticatory cycles is associated with reduced appetite and altered postprandial plasma concentrations of gut hormones, insulin and glucose

To determine the influence of masticatory efficiency on postprandial satiety and glycaemic response, twenty-one healthy males were recruited for this randomised cross-over trial. The participants consumed a fixed amount of pizza provided in equal-sized portions by chewing each portion either fifteen or forty times before swallowing. Subjective appetite was measured by appetite questionnaires at regular intervals for 3 h after the meal and plasma samples were collected for the measurement of selected satiety-related hormones, glucose, insulin and glucose-dependent insulinotropic peptide (GIP) concentrations. An ad libitum meal was provided shortly after the last blood sample was drawn and the amount eaten recorded. Compared with fifteen chews, chewing forty times per portion resulted in lower hunger (P= 0·009), preoccupation with food (P= 0·005) and desire to eat (P= 0·002). Meanwhile, plasma concentrations of glucose (P= 0·024), insulin (P< 0·001) and GIP (P< 0·001) were higher following the forty-chews meal. Chewing forty times before swallowing also resulted in a higher plasma cholecystokinin concentration (P= 0·045) and a trend towards a lower ghrelin concentration (P= 0·051). However, food intake at the subsequent test meal did not differ (P= 0·851). The results suggest that a higher number of masticatory cycles before swallowing may provide beneficial effects on satiety and facilitate glucose absorption.

Long-term results of a randomized clinical trial comparing Roux-en-Y gastric bypass with vertical banded gastroplasty

The long-term results of Roux-en-$\hbox{Y}$ gastric bypass (gastric bypass) and vertical banded gastroplasty (VBG) from randomized studies have not been described in detail. Patients were randomized to gastric bypass or VBG. Body mass index (BMI), body composition, eating habits and gastrointestinal hormones were reviewed after 6 years. The frequency of reoperation was assessed up to 10 years after surgery. Sixty-six (80 per cent) of the 82 subjects randomized were assessed for weight and BMI 6 years after surgery, 30 (81 per cent) in the gastric bypass group and 36 (80 per cent) in the VBG group. Intention-to-treat analysis demonstrated greater weight loss after gastric bypass compared with VBG, 6 years after surgery: BMI reduced from 41·8 (95 per cent confidence interval 41·3 to 42·3) to 30·3 (28·6 to 32·0) kg/m(2) for gastric bypass and from 42·3 (42·8 to 44·8) to 32·9 (31·3 to 34·5) kg/m(2) for VBG (P = 0·036). Gastric bypass caused a larger loss of fat mass (P = 0·026) and better preservation of lean tissue (P = 0·009). Patients having a gastric bypass had greater postprandial responses to the satiety hormones glucagon-like peptide 1 and peptide YY (P = 0·003 and P = 0·004 respectively). Ghrelin levels did not differ between the groups. Patients with a gastric bypass maintained a lower intake of fat compared with those having VBG (P = 0·013). Some 89 per cent of patients who initially had VBG had undergone, or were scheduled for, conversion to gastric bypass at latest follow-up. Gastric bypass was superior to VBG regarding weight loss, body composition, dietary composition and postprandial satiety hormone responses.

A role for endogenous peptide YY in tachykinin NK2 receptor‐triggered 5‐HT release from guinea pig isolated colonic mucosa

The colon-derived peptide hormone, peptide YY (PYY), regulates colonic motility, secretion and postprandial satiety; but little is known about the influence of endogenous PYY on 5-HT release from colonic mucosa. Tachykinin NK(2) receptor-selective agonist, βAla-NKA-(4-10) induces 5-HT release from guinea pig colonic mucosa via NK(2) receptors on the mucosal layer. The present study was designed to determine the influence of endogenous PYY on 5-HT release from guinea pig colonic mucosa, evoked by the NK(2) receptor agonist, βAla-NKA-(4-10). Muscle layer-free mucosal preparations of guinea pig colon were incubated in vitro and the outflow of PYY or 5-HT and its metabolite, 5-HIAA, from these preparations were determined by enzyme immunoassays or HPLC with electrochemical detection respectively. βAla-NKA-(4-10) produced a tetrodotoxin-resistant sustained increase in the outflow of PYY and 5-HT from the mucosal preparations. The βAla-NKA-(4-10)-evoked 5-HT outflow was partially inhibited by Y(1) receptor antagonist, BIBO3304, and Y(2) receptor antagonist, BIIE0246, but with less potency. Exogenously-applied PYY also produced a sustained increase in the outflow of 5-HT that was inhibited by Y(1) blockade but not Y(2) blockade. Our findings support the view that the NK(2) receptor-selective agonist, βAla-NKA-(4-10) produces a long-lasting PYY release from guinea pig colonic mucosa via NK(2) receptors on L cells and βAla-NKA-(4-10)-evoked 5-HT release is in part mediated by endogenously released PYY, acting mainly on Y(1) receptors on EC cells. The PYY-containing L cells appear to play a role in controlling the release of 5-HT from colonic EC cells.

Abstract 199: Hydrogen Peroxide Mediates the pH Conditioned Chloride Conductance in Nodose Ganglia Neurons

pH sensitivity has been rarely studied in vagal afferents of nodose ganglia (NG) neurons. Using whole-cell patch-clamp technique in isolated NG neurons, we recently identified a pH-conditioned Cl - current (pH-I) that was evoked following 2 or 3 brief (10s) exposures to low extracellular pH (7.0-6.0) in 16 of 22 (70%) cells (FASEB J, 2012). The current is large (904.3±159.9pA) and prolonged, lasting 10∼15 minutes, and causes significant depolarization (Δ35.2±4.4mV). In the present study, we tested the hypothesis that reactive oxygen species (ROS) mediates this pH-conditioned Cl - conductance. We found that the rate of increase in fluorescence [(F-F 0 )/F 0 ] of NG neurons loaded with dihydroethidine (ROS dye) rose dramatically following the brief exposures to pH 6.0 from a control of 0.04±0.01 to 0.12±0.02 units/min over 10∼15 minutes (n=31 neurons, p&lt;0.01). Moreover superfusion of neurons with H 2 O 2 induced currents that mimicked the pH conditioned currents. Because of similarities between the pH-conditioned Cl - conductance and the previously described “swell-activated” Cl - current induced with hypoosmotic solutions, we superfused the NG neurons with the H 2 O 2 scavenger PEG-catalase (1000 units/ml). PEG-catalase blocked significantly (p&lt;0.01) the “swell” response to 210 mOsm from 23.3±6.3pA/pF to 0.57±0.39 pA/pF (n=4) as well as the pH-conditioned response from 25.7±6.5pA/pF (n=6) to 6.9±1.4 pA/pF (n=12). The superoxide scavenger PEG-SOD did not affect the current. These results indicate that both pH-conditioned and swell-induced responses are mediated by H 2 O 2 . Opening of these outward Cl - conductances that cause sustained depolarization of vagal afferents may induce a beneficial reflex sympathoinhibition during myocardial ischemia/acidosis or initiate a gastro-intestinal post-prandial satiety reflex.