Cholecystokinin regulates satiation idependently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy
Ripken, D. ; Wielen, N. van der; Meulen, J. van der; Schuurman, T. ; Witkamp, R.F. ; Hendriks, H.F.J. ; Koopmans, S.J. - \ 2015
Physiology and Behavior 139 (2015)2015. - ISSN 0031-9384 - p. 167 - 176.
glucagon-like peptide-1 - food-intake - paracetamol absorption - physiological-role - appetite control - exendin 9-39 - rats - glp-1 - antagonist - afferents
The vagal nerve and gut hormones CCK and GLP-1 play important roles in the control of food intake. However, it is not clear to what extent CCK and GLP-1 increase satiation by stimulating receptors located on abdominal vagal nerve endings or via receptors located elsewhere. This study aimed to further explore the relative contribution of the abdominal vagal nerve in mediating the satiating effects of endogenous CCK and GLP-1. Total subdiaphragmatic vagotomy or sham operation was combined with administration of CCK1 and GLP-1 receptor antagonists devazepide and exendin (9–39) in 12 pigs, applying an unbalanced Latin Square within-subject design. Furthermore, effects of vagotomy on preprandial and postprandial acetaminophen absorption, glucose, insulin, GLP-1 and CCK plasma concentrations were investigated. Ad libitum liquid meal intake (mean ± SEM) was similar in sham and vagotomized pigs (4180 ± 435 and 3760 ± 810 g/meal). Intake increased by about 20% after blockade of CCK1 receptors, independently of the abdominal vagal nerve. Food intake did not increase after blockade of GLP-1 receptors. Blockade of CCK1 and GLP-1 receptors increased circulating CCK and GLP-1 concentrations in sham pigs only, suggesting the existence of a vagal reflex mechanism in the regulation of plasma CCK1 and GLP-1 concentrations. Vagotomy decreased acetaminophen absorption and changed glucose, insulin, CCK and GLP-1 concentrations indicating a delay in gastric emptying. Our data show that at liquid feeding, satiation is decreased effectively by pharmacological blockade of CCK1 receptors. We conclude that regulation of liquid meal intake appears to be primarily regulated by CCK1 receptors not located on abdominal vagal nerve endings.
Ileal brake activation: macronutrient-specific effects on eating behavior?
Avesaat, M. van; Troost, F.J. ; Ripken, D. ; Hendriks, H.F. ; Masclee, A.A.M. - \ 2015
International Journal of Obesity 39 (2015). - ISSN 0307-0565 - p. 235 - 243.
glucagon-like peptide-1 - food-intake - hormone-release - energy-intake - antropyloroduodenal motility - gastrointestinal hormones - intestinal motility - duodenal glucose - plasma-levels - healthy-men
Background:Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown.Objective:The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control.Design:This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4¿kg¿m-2) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7¿kcal), low-dose casein ((LP) 17.2¿kcal) or high-dose casein ((HP) 51.7¿kcal), low-dose sucrose ((LC) 17.2¿kcal) and high-dose sucrose ((HC) 51.7¿kcal), over a period of 90¿min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals.Results:Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7¿kcal, P
Cross-Species Comparison of Genes Related to Nutrient Sensing Mechanisms Expressed along the Intestine
Wielen, N. van der; Avesaat, M. van; Wit, N.J.W. de; Vogels, J. ; Troost, F. ; Masclee, A. ; Koopmans, S.J. ; Meulen, J. van der; Boekschoten, M.V. ; Müller, M.R. ; Hendriks, H.F.J. ; Witkamp, R.F. ; Meijerink, J. - \ 2014
PLoS ONE 9 (2014)9. - ISSN 1932-6203 - 9 p.
glucagon-like peptide-1 - h+/peptide transporter pept1 - glucose cotransporter sglt1 - dietary-regulation - molecular-mechanisms - receptor expression - sucrase-isomaltase - hormone-secretion - taste receptors - induced obesity
Introduction Intestinal chemosensory receptors and transporters are able to detect food-derived molecules and are involved in the modulation of gut hormone release. Gut hormones play an important role in the regulation of food intake and the control of gastrointestinal functioning. This mechanism is often referred to as “nutrient sensing”. Knowledge of the distribution of chemosensors along the intestinal tract is important to gain insight in nutrient detection and sensing, both pivotal processes for the regulation of food intake. However, most knowledge is derived from rodents, whereas studies in man and pig are limited, and cross-species comparisons are lacking. Aim To characterize and compare intestinal expression patterns of genes related to nutrient sensing in mice, pigs and humans. Methods Mucosal biopsy samples taken at six locations in human intestine (n = 40) were analyzed by qPCR. Intestinal scrapings from 14 locations in pigs (n = 6) and from 10 locations in mice (n = 4) were analyzed by qPCR and microarray, respectively. The gene expression of glucagon, cholecystokinin, peptide YY, glucagon-like peptide-1 receptor, taste receptor T1R3, sodium/glucose cotransporter, peptide transporter-1, GPR120, taste receptor T1R1, GPR119 and GPR93 was investigated. Partial least squares (PLS) modeling was used to compare the intestinal expression pattern between the three species. Results and conclusion The studied genes were found to display specific expression patterns along the intestinal tract. PLS analysis showed a high similarity between human, pig and mouse in the expression of genes related to nutrient sensing in the distal ileum, and between human and pig in the colon. The gene expression pattern was most deviating between the species in the proximal intestine. Our results give new insights in interspecies similarities and provide new leads for translational research and models aiming to modulate food intake processes in man.
Review article: the role of gastrointestinal hormones in the treatment of delayed gastric emptying in critically ill patients
Luttikhold, J. ; Ruijter, F.M. de; Norren, K. van; Diamant, M. ; Witkamp, R.F. ; Leeuwen, P.A.M. ; Vermeulen, M.A.R. - \ 2013
Alimentary Pharmacology and Therapeutics 38 (2013)6. - ISSN 0269-2813 - p. 573 - 583.
glucagon-like peptide-1 - motilin receptor agonist - placebo-controlled trial - early enteral nutrition - body-weight gain - diabetic gastroparesis - pancreatic-polypeptide - double-blind - food-intake - acid-secretion
Background The role of diet in inflammatory bowel disease (IBD) is supported by migration studies and increasing incidences in line with Westernisation. Aim To give a complete overview of studies associating habitual diet with the onset or relapses in ulcerative colitis (UC) or Crohn's disease (CD). Methods A structured search in Pubmed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers in English language. Results Forty-one studies were identified, investigating onset (n = 35), relapses (n = 5) or both (n = 1). Several studies reported high intake of sugar or sugar-containing foods (n = 7 UC, n = 12 CD), and low intake of fruits and/or vegetables (n = 5 UC, n = 10 CD) to be associated with an increased onset risk. However, these findings could not be confirmed by similar or higher numbers of other studies. A possible protective role was found for grain-derived products in CD onset, but results were inconsistent for dietary fibre in UC and CD and grain-derived products in UC. No definite conclusions could be drawn for unsaturated fatty acids (UFA), protein and energy intake due to limited and/or inconsistent results. Six studies reported on diet and relapse risk, of which only two (n = 1 UC, n = 1 CD) had a prospective follow-up. Conclusions The current evidence is not sufficient to draw firm conclusions on the role of specific food components or nutrients in the aetiology of IBD. Furthermore, large prospective studies into the role of habitual diet as a trigger of relapses are needed, to identify new therapeutic or preventive targets
Potential benefits of satiety to the consumer: scientific considerations
Hetherington, M.M. ; Cunningham, K. ; Dye, L. ; Gibson, E.L. ; Gregersen, N.T. ; Halford, J.C.G. ; Lawton, C.L. ; Lluch, A. ; Mela, D.J. ; Trijp, J.C.M. van - \ 2013
Nutrition Research Reviews 26 (2013). - ISSN 0954-4224 - p. 22 - 38.
low-calorie diet - high-protein-diet - body-weight loss - disentangling food reward - sensory-specific satiety - glucagon-like peptide-1 - cognitive performance - energy-intake - appetite sensations - eating behavior
Foods and dietary patterns that enhance satiety may provide benefit to consumers. The aim of the present review was to describe, consider and evaluate research on potential benefits of enhanced satiety. The proposal that enhanced satiety could only benefit consumers by a direct effect on food intake should be rejected. Instead, it is proposed that there is a variety of routes through which enhanced satiety could (indirectly) benefit dietary control or weight-management goals. The review highlights specific potential benefits of satiety, including: providing appetite control strategies for consumers generally and for those who are highly responsive to food cues; offering pleasure and satisfaction associated with low-energy/healthier versions of foods without feeling ‘deprived’; reducing dysphoric mood associated with hunger especially during energy restriction; and improved compliance with healthy eating or weight-management efforts. There is convincing evidence of short-term satiety benefits, but only probable evidence for longer-term benefits to hunger management, possible evidence of benefits to mood and cognition, inadequate evidence that satiety enhancement can promote weight loss, and no evidence on which consumers would benefit most from satiety enhancement. The appetite-reducing effects of specific foods or diets will be much more subtle than those of pharmaceutical compounds in managing hunger; nevertheless, the experience of pharmacology in producing weight loss via effects on appetite suggests that there is potential benefit of satiety enhancement from foods incorporated into the diet to the consumer.
A diet high in resistant starch modulates microbiota composition, SCFA concentrations, and gene expression in pig intestine
Haenen, D. ; Zhang, J. ; Souza Da Silva, C. ; Bosch, G. ; Meer, I.M. van der; Arkel, J. van; Borne, J.J.G.C. van den; Pérez Gutiérrez, O. ; Smidt, H. ; Kemp, B. ; Müller, M.R. ; Hooiveld, G.J.E.J. - \ 2013
The Journal of Nutrition 143 (2013)3. - ISSN 0022-3166 - p. 274 - 283.
chain fatty-acids - glucagon-like peptide-1 - phylogenetic microarray - gastrointestinal-tract - human gut - appetite regulation - metabolic syndrome - colonic function - us adults - body-fat
Resistant starch (RS) is highly fermentable by microbiota in the colon, resulting in the production of SCFAs. RS is thought to mediate a large proportion of its health benefits, including increased satiety, through the actions of SCFAs. The aim of this study was to investigate the effects of a diet high in RS on luminal microbiota composition, luminal SCFA concentrations, and the expression of host genes involved in SCFA uptake, SCFA signaling, and satiety regulation in mucosal tissue obtained from small intestine, cecum, and colon. Twenty adult female pigs were either assigned to a digestible starch (DS) diet or a diet high in RS (34%) for a period of 2 wk. After the intervention, luminal content and mucosal scrapings were obtained for detailed molecular analysis. RS was completely degraded in the cecum. In both the cecum and colon, differences in microbiota composition were observed between DS- and RS-fed pigs. In the colon these included the stimulation of the healthy gut-associated butyrate-producing Faecalibacterium prausnitzii, whereas potentially pathogenic members of the Gammaproteobacteria, including Escherichia coli and Pseudomonas spp., were reduced in relative abundance. Cecal and colonic SCFA concentrations were significantly greater in RS-fed pigs, and cecal gene expression of monocarboxylate transporter 1 (SLC16A1) and glucagon (GCG) was induced by RS. In conclusion, our data show that RS modulates microbiota composition, SCFA concentrations, and host gene expression in pig intestine. Combined, our data provide an enhanced understanding of the interaction between diet, microbiota, and host
Effects of dietary fibers with different fermentation characteristics on feeding motivation in adult female pigs
Souza Da Silva, C. ; Bolhuis, J.E. ; Gerrits, W.J.J. ; Kemp, B. ; Borne, J.J.G.C. van den - \ 2013
Physiology and Behavior 110-111 (2013). - ISSN 0031-9384 - p. 148 - 157.
chain fatty-acids - glucagon-like peptide-1 - resistant starch - growing pigs - appetite regulation - guar gum - gastrointestinal peptides - nonstarch polysaccharides - hindgut fermentation - weight regulation
Dietary fibers can be fermented in the colon, resulting in production of short-chain fatty acids (SCFA) and secretion of satiety-related peptides. Fermentation characteristics (fermentation kinetics and SCFA-profile) differ between fibers and could impact their satiating potential. We investigated the effects of fibers with varying fermentation characteristics on feeding motivation in adult female pigs. Sixteen pair-housed pigs received four diets in four periods in a Latin square design. Starch from a control (C) diet was exchanged, based on gross energy, for inulin (INU), guar gum (GG), or retrograded tapioca starch (RS), each at a low (L) and a high (H) inclusion level. This resulted in a decreased metabolizable energy intake when feeding fiber diets as compared with the C diet. According to in vitro fermentation measurements, INU is rapidly fermentable and yields relatively high amounts of propionate, GG is moderately rapidly fermentable and yields relatively high amounts of acetate, and RS is slowly fermentable and yields relatively high amounts of butyrate. Feeding motivation was assessed using behavioral tests at 1 h, 3 h and 7 h after the morning meal, and home pen behavioral observations throughout the day. The number of wheel turns paid for a food reward in an operant test was unaffected by diet. Pigs on H-diets ran 25% slower for a food reward in a runway test than pigs on L-diets, and showed less spontaneous physical activity and less stereotypic behavior in the hours before the afternoon meal, reflecting increased interprandial satiety. Reduced feeding motivation with increasing inclusion level was most pronounced for RS, as pigs decreased speed in the runway test and tended to have a lower voluntary food intake in an ad libitum food intake test when fed RS-H. In conclusion, increasing levels of fermentable fibers in the diet seemed to enhance satiety in adult pigs, despite a reduction in metabolizable energy supply. RS was the most satiating fiber, possibly due to its slow rate of fermentation and high production of butyrate
Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women
Dewulf, E.M. ; Cani, P.D. ; Claus, S.P. ; Fuentes, S. ; Puylaert, P.G.B. ; Neyrinck, A.M. ; Bindels, L.B. ; Vos, W.M. de; Gibson, G.R. ; Thissen, J.P. ; Delzenne, N.M. - \ 2013
Gut 62 (2013)8. - ISSN 0017-5749 - p. 1112 - 1121.
glucagon-like peptide-1 - high-fat-diet - oligofructose promotes satiety - human colonic microbiota - induced weight-loss - gut microbiota - insulin-resistance - bacteroides-vulgatus - fecal microbiota - lipid-metabolism
OBJECTIVE: To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. METHODS: A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by (1)H-NMR spectroscopy. RESULTS: Treatment with ITF prebiotics, but not the placebo, led to an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes. CONCLUSIONS: ITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures
Effects of Long- and Short-Chain Fatty Acids on the Release of Gastrointestinal Hormones using an ex Vivo Porcine Intestinal Tissue Model
Voortman, T. ; Hendriks, H.F.J. ; Witkamp, R.F. ; Wortelboer, H.M. - \ 2012
Journal of Agricultural and Food Chemistry 60 (2012)36. - ISSN 0021-8561 - p. 9035 - 9042.
glucagon-like peptide-1 - enteroendocrine cell-line - food-intake - cholecystokinin secretion - glucose-homeostasis - yy - glp-1 - humans - stimulation - protein
Gastrointestinal (GI) peptide hormones play an important role in short-term regulation of food intake and blood glucose levels. Modulating their release is of potential relevance for weight management and possibly diabetes. As currently available models are hard to extrapolate to the human situation, the use of porcine intestinal tissue, collected from slaughter pigs, was investigated for this purpose. Intestinal tissue disks showed a predicted regional release pattern of GI peptides. Various long-chain fatty acids differentially stimulated release of glucagon-like peptide 1 (GLP-1) (up to 500%) and glucagon-like peptide 2 (GLP-2) (up to 200%) from ileal tissue disks, but effects on peptide YY (PYY) did not reach significance. Short-chain fatty acids had no effects on the release of GLP-1, GLP-2, and PYY in either the ileum or colon. In conclusion, this porcine tissue model shows to be of advantageous use in a tiered approach to study the potential of satiety-inducing compounds to be selected for studies in humans.
Use of satiety peptides in assessing the satiating capacity of foods
Mars, M. ; Stafleu, A. ; Graaf, C. de - \ 2012
Physiology and Behavior 105 (2012)2. - ISSN 0031-9384 - p. 483 - 488.
glucagon-like peptide-1 - energy-intake - promotes satiety - obese subjects - healthy-men - appetite - humans - cholecystokinin - glp-1 - pyy3-36
Foods differ in their satiating capacity. Satiety peptides may help to provide evidence for biological mechanisms behind these differences. The aim of this paper was to discuss the physiological relevance of three individual appetite peptides, i.e. CCK, GLP-1 and PYY, in assessing the satiating capacity of foods. A literature research was conducted on CCK, GLP-1, PYY and satiety; effective exogenous infusion studies and endogenous production studies, i.e. changes induced by foods, were identified. The relative changes in blood concentrations in these studies were compared in order to assess an indication of the physiological relevance of the peptides. Relative changes in the two types of studies investigating CCK overlapped, i.e. increases in serum were 3 to 14-fold in effective exogenous studies (n = 7) and 2 to 8-fold in endogenous production studies (n = 9). The relative changes in GLP-1 and PYY did not overlap; GLP-1: 4 to 16 fold in effective exogenous studies (n = 4) and no effect to 4 fold in endogenous production studies (n = 38). PYY: 3 to 11-fold in effective exogenous studies (n = 14) and no effect to 2-fold in endogenous production studies (n = 10). GLP-1 and PYY show effects on satiety at supra-physiological dosages, they are not likely to contribute individually to a difference in satiating capacity of foods and can therefore not be interpreted in isolation. The effects of CCK are likely to be in the physiological range and therefore may have an individual contribution to a difference in satiating capacity between foods
Successful development of satiety enhancing food products: towards a multidisciplinary agenda of research challenges
Kleef, E. van; Trijp, J.C.M. van; Borne, J.J.G.C. van den; Zondervan, C. - \ 2012
Critical Reviews in Food Science and Nutrition 52 (2012)7. - ISSN 1040-8398 - p. 611 - 628.
sensory-specific satiety - glucagon-like peptide-1 - energy-intake - portion size - functional foods - dietary fiber - weight management - low-fat - consumption volume - metabolic syndrome
In the context of increasing prevalence of overweight and obesity in societies worldwide, enhancing the satiating capacity of foods may help people control their energy intake and weight. This requires an integrated approach between various food related disciplines. By structuring this approach around the new product development process, this paper aims to present the contours of such an integrative approach by going through the current state of the art around satiety enhancing foods. It portrays actual food choice as the end result of a complex interaction between internal satiety signals, other food benefits and environmental cues. Three interrelated routes to satiating enhancement are (1) change food composition to develop stronger physiological satiation and satiety signals, (2) anticipate and build on smart external stimuli at moment of purchase and consumption, and (3) improve palatability and acceptance of satiety enhanced foods. Key research challenges in achieving those routes in the field of nutrition, food technology, consumer, marketing and communication are outlined
Presence, formation and putative biological activities of N-acyl serotonins, a novel class of fatty-acid derived mediators in the intestinal tract
Verhoeckx, K.C.M. ; Voortman, T. ; Balvers, M.G.J. ; Hendriks, H.F.J. ; Wortelboer, H.M. ; Witkamp, R.F. - \ 2011
Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids 1811 (2011)10. - ISSN 1388-1981 - p. 578 - 586.
glucagon-like peptide-1 - rat-brain - arachidonoyl-serotonin - endocannabinoid inactivation - electrospray-ionization - quantitative method - mass-spectrometry - amide hydrolase - anandamide - analogs
Following the discovery of the endocannabinoid arachidonoyl ethanolamide (anandamide) and other N-acyl-ethanolamines, several other compounds have been found in which amino acids or neurotransmitters rather than ethanolamide are linked to fatty acids. Studies have shown that the local availability of fatty acid precursors, which in turn is modulated by dietary intake of lipids, determines the pattern of conjugates formed. Less information is available whether the same might be true for the amines or neurotransmitters involved. We hypothesized that N-arachidonoyl-serotonin (AA-5-HT) and its analogs could be endogenously present in those tissues that have high contents of serotonin. We investigated the endogenous presence of N-acyl serotonins in different parts of the gastro-intestinal tract of pigs and mice. We discovered that AA-5-HT, oleoyl-serotonin, palmitoyl-serotonin, and stearoyl-serotonin were endogenously present, particularly in the jejunum and ileum. Their formation in vitro was stimulated by the addition of serotonin to intestinal tissue incubations. Furthermore, in a mouse study we showed that the pattern of formation is dependent on the relative amount of fatty acids in the diet. The formation of docosahexaenoyl-serotonin and eicosapentaenoyl-serotonin was elevated in mice fed with a diet containing fish oil. Preliminary data showed that several of the serotonin conjugates are able to inhibit glucagon-like peptide-1 secretion and FAAH activity in vitro. Taken together, our data suggest that N-acyl serotonins are a novel class of lipid mediators present in the gut with highly promising biological properties
Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice
Everard, A. ; Derrien, M.M.N. ; Possemiers, S. ; Vos, W.M. de; Delzenne, N.M. ; Schrenzel, J. ; Cani, P.D. - \ 2011
Diabetes 60 (2011)11. - ISSN 0012-1797 - p. 2775 - 2786.
glucagon-like peptide-1 - inulin-type fructans - phylogenetic microarray - insulin-resistance - inflammation - permeability - endotoxemia - mechanism - rats - adipogenesis
OBJECTIVE To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice. RESEARCH DESIGN AND METHODS Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models. RESULTS In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat-fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters. CONCLUSIONS We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes
Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?
Diamant, M. ; Vaughan, E.E. ; Vos, W.M. de - \ 2011
Obesity Reviews 12 (2011)4. - ISSN 1467-7881 - p. 272 - 281.
glucagon-like peptide-1 - gastrointestinal-tract microbiota - protein-coupled receptor - human colonic microbiota - chain fatty-acids - healthy humans - adipose-tissue - double-blind - weight-loss - akkermansia-muciniphila
The current obesity and type 2 diabetes pandemics have causes beyond changes in eating and exercise habits against a susceptible genetic background. Gut bacteria seem to additionally contribute to the differences in body weight, fat distribution, insulin sensitivity and glucose- and lipid-metabolism. Data, mostly derived from preclinical studies, suggest that gut microbiota play an important role in conditions such as obesity, diabetes, metabolic syndrome and non-alcoholic fatty liver disease. Regulation of energy uptake from the gut, by digesting otherwise indigestible common polysaccharides in our diet, production or activation of signalling molecules involved in host metabolism, modification of gut permeability, the release of gut hormones and inflammation, are among the mechanisms by which gut microbiota may influence the host cardiometabolic phenotype. Recent evidence suggests that quantitative and qualitative differences in gut microbiota exist between lean and obese, and between diabetic and non-diabetic individuals. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may favourably affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are eagerly awaited
Gastrointestinal targets of appetite regulation in humans
Delzenne, N.M. ; Blundell, J.E. ; Brouns, F. ; Cunningham, K. ; Graaf, C. de; Erkner, A. ; Lluch, A. ; Mars, M. ; Peters, H.P.F. ; Westerterp-Plantenga, M. - \ 2010
Obesity Reviews 11 (2010)3. - ISSN 1467-7881 - p. 234 - 250.
glucagon-like peptide-1 - acid breath test - aqueous meal components - plasma ghrelin levels - libitum energy-intake - cholecystokinin receptor antagonist - c-terminal octapeptide - high-carbohydrate meal - increases food-intake - gastric-emptying rate
The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions – and related biomarkers – implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon-like peptide, peptide tyrosin-tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.
The environment within: how gut microbiota may influence metabolism and body composition
Vrieze, A. ; Holleman, F. ; Zoetendal, E.G. ; Vos, W.M. de; Hoekstra, J.B. ; Nieuwdorp, M. - \ 2010
Diabetologia 53 (2010)4. - ISSN 0012-186X - p. 606 - 613.
glucagon-like peptide-1 - diet-induced obesity - y gastric bypass - dependent insulinotropic polypeptide - type-2 diabetes-mellitus - glucose-tolerance - incretin levels - weight-loss - fed infants - secretion
Obesity, diabetes and consequently atherosclerotic vascular disease have become major health and public health issues worldwide. The increasing and staggering prevalence of obesity might not only be explained by nutritional habits or the reduction of energy expenditure through decreased physical activity. In addition, recent studies have focused on intestinal microbiota as environmental factors that increase energy yield from diet, regulate peripheral metabolism and thereby increase body weight. Obesity is associated with substantial changes in composition and metabolic function of gut microbiota, but the pathophysiological processes driving this bidirectional relationship have not been fully elucidated. This review discusses the relationships between the following: composition of gut microbiota, energy extracted from diet, synthesis of gut hormones involved in energy homeostasis, production of butyrate and the regulation of fat storage
Effect of dietary fibre type on physical activity and behaviour in kennelled dogs
Bosch, G. ; Beerda, B. ; Hoek, E. van de; Hesta, M. ; Poel, A.F.B. van der; Janssens, G.P.J. ; Hendriks, W.H. - \ 2009
Applied Animal Behaviour Science 121 (2009)1. - ISSN 0168-1591 - p. 32 - 41.
glucagon-like peptide-1 - in-vitro fermentation - gastrointestinal-tract - spatial restriction - chronic stress - pregnant sows - food-intake - responses - ghrelin - satiety
Dog diets may differ in their effectiveness of maintaining satiety after a meal. Consequently, sensations of hunger, feeding motivation, physical activity, and sensitivity to environmental stressors may be increased. Dietary fibre may be effective in prolonging postprandial satiety depending on type and inclusion level. This study evaluated the effect of fibre fermentability on behaviour in dogs. Sixteen healthy adult dogs were housed individually and fed a low-fermentable fibre (LFF) diet containing 8.5% cellulose or a high-fermentable fibre (HFF) diet containing 8.5% sugar beet pulp and 2% inulin. Dogs were fed two equal portions at 8:30 and 18:30 according to energy requirements. Behaviour of dogs in their home-cage was recorded and analyzed by instantaneous scan sampling (2 × 24 h with 15 min intervals) and focal sampling continuous recordings (10 min per animal per hour, from 9:00 until 18:00). Dogs were subjected to a behaviour test composed of the subtests open-field, sudden-silence, novel-object, and acoustic-startle. The behavioural responses of each dog were recorded. Scores for the scan and focal samples were expressed per clock hour and DIET × TIME effects were tested statistically using Residual Maximum Likelihood (REML). Data from the tests were examined using principal component analysis resulting in the compilation of two components. Data were tested statistically for DIET and DIET × SUBTEST effects using REML. Variables specific for the open-field and novel-object test were analyzed using analysis of variance. For the scans, a significant DIET × TIME effect was found for resting. At night and in the morning, HFF dogs rested more compared to LFF dogs, but they rested less between 14:00 and 17:00. For the continuous recordings, the main findings were a tendency for DIET × TIME effect for time spent resting with a pattern consistent with that for the scans. The interaction was significant for inactive-alert (lie with head up or sitting) with HFF-fed dogs having lower values around 10:00–11:00 and higher values hereafter. Finally, time spent tail wagging was significantly higher for LFF-fed dogs just before the evening meal that may indicate higher level of arousal. For the behaviour tests, no significant DIET or DIET × SUBTEST effects were detected. It is concluded that compared to the LFF diet, the HFF diet increased inactivity in kennelled beagle dogs likely through the prolongation of postprandial satiety. This effect did not change the reaction to stressful events in kennelled laboratory dogs. Enhanced susceptibility to environmental stressors at times of hunger in sensitive companion dogs may occur but requires further study
The effects of dietary fibre type on satiety-related hormones and voluntary food intake in dogs
Bosch, G. ; Verbrugghe, A. ; Hesta, M. ; Holst, J.J. ; Poel, A.F.B. van der; Janssens, G.P.J. ; Hendriks, W.H. - \ 2009
The British journal of nutrition 102 (2009)2. - ISSN 0007-1145 - p. 318 - 325.
glucagon-like peptide-1 - in-vitro fermentation - gastrointestinal peptides - titanium-dioxide - detergent fiber - plasma ghrelin - blood-glucose - healthy dogs - high-protein - fatty-acids
Depending on type and inclusion level, dietary fibre may increase and maintain satiety and postpone the onset of hunger. This 7-week study evaluated the effect of fibre fermentability on physiological satiety-related metabolites and voluntary food intake (VFI) in dogs. Sixteen healthy adult dogs were fed a low-fermentable fibre (LFF) diet containing 8·5 % cellulose or a high-fermentable fibre (HFF) diet containing 8·5 % sugarbeet pulp and 2 % inulin. Large intestinal fibre degradation was evaluated by apparent faecal digestibility of nutrients and faecal SCFA and NH3 concentrations. Postprandial blood samples were obtained to determine postprandial plasma glucose, insulin, total peptide tyrosine–tyrosine (PYY), total glucagon-like peptide-1 (GLP-1) and total ghrelin concentrations. At the end of the study, the dogs were given a single meal of a dry dog food to determine VFI. Dogs fed the HFF diet had a significantly higher large intestinal fibre degradation and production of SCFA compared with the dogs fed the LFF diet. The HFF-fed dogs tended (P = 0·058) to show a lower VFI at the end of the study. No treatment effects were found for postprandial plasma glucose, PYY, GLP-1 and ghrelin responses. The concentrations of these metabolites could not be related to the observed difference in VFI. The inclusion of fermentable fibre in canine diets may contribute to the prevention or mitigation of obesity through its effects on satiety. The underlying mechanisms require further investigation
Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion
Smeets, P.A.M. ; Vidarsdottir, S. ; Graaf, C. de; Stafleu, A. ; Osch, M.J.P. ; Viergever, M.A. ; Pijl, H. ; Grond, J. van der - \ 2007
American Journal of Physiology. Endocrinology and Metabolism 293 (2007)3. - ISSN 0193-1849 - p. E754 - E758.
glucagon-like peptide-1 - central-nervous-system - reduces food-intake - postprandial glucose - sensory stimulation - insulin release - functional mri - blood-glucose - sweet taste - body-weight
Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion. Am J Physiol Endocrinol Metab 293: E754-E758, 2007. First published June 12, 2007; doi:10.1152/ajpendo.00231.2007. - We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent ( BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load, we here compare hypothalamic BOLD signal changes subsequent to an oral vs. an intravenous (iv) glucose challenge in healthy humans. Seven healthy, normal-weight men received four interventions in random order after an overnight fast: 1) ingestion of glucose solution ( 75 g in 300 ml) or 2) water ( 300 ml), and 3) iv infusion of 40% glucose solution (0.5 g/kg body wt, maximum 35 g) or 4) infusion of saline (0.9% NaCl, equal volume). The BOLD signal was recorded as of 8 min prior to intervention ( baseline) until 30 min after. Glucose infusion was associated with a modest and transient signal decline in the hypothalamus. In contrast, glucose ingestion was followed by a profound and persistent signal decrease despite the fact that plasma glucose levels were almost threefold lower than in response to iv administration. Accordingly, glucose ingestion tended to suppress hunger more than iv infusion ( P <0.1). We infer that neural and endocrine signals emanating from the gastrointestinal tract are critical for the hypothalamic response to nutrient ingestion.
Effects of gastric emptying on the postprandial ghrelin response
Blom, W.A.M. ; Lluch, A. ; Vinoy, S. ; Stafleu, A. ; Berg, R. van den; Holst, J.J. ; Kok, F.J. ; Hendriks, H.F.J. - \ 2006
American Journal of Physiology. Endocrinology and Metabolism 290 (2006)2. - ISSN 0193-1849 - p. E389 - E395.
glucagon-like peptide-1 - acylated ghrelin - food-intake - inhibitory polypeptide - paracetamol absorption - nonacylated ghrelin - circulating ghrelin - insulin - humans - secretion
Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion (P <0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = ¿0.76; 95% CI = ¿0.90, ¿0.49, GLP-1 r = ¿0.47; 95% CI = ¿0.76, ¿0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = ¿0.36; 95% CI = ¿0.69, 0.09; GLP- 1 r = ¿0.42; 95% CI = ¿0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = ¿0.74; 95% CI= ¿0.89, ¿0.45; GLP-1 r = ¿0.63; 95% CI = ¿0.84, ¿0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion