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Gastrointestinal motility, gut hormone secretion, and energy intake after oral loads of free fatty acid or triglyceride in older and middle-aged men.
Madsen, JL, Damgaard, M, Fuglsang, S, Dirksen, C, Holst, JJ, Graff, J
Appetite. 2019;:18-24
Abstract
In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ± 3.4 (mean ± SD) years) and 10 middle-aged (age 43.1 ± 8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p < 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p < 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p < 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.
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Mechanisms controlling hormone secretion in human gut and its relevance to metabolism.
Martin, AM, Sun, EW, Keating, DJ
The Journal of endocrinology. 2019;(1):R1-R15
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Abstract
The homoeostatic regulation of metabolism is highly complex and involves multiple inputs from both the nervous and endocrine systems. The gut is the largest endocrine organ in our body and synthesises and secretes over 20 different hormones from enteroendocrine cells that are dispersed throughout the gut epithelium. These hormones include GLP-1, PYY, GIP, serotonin, and CCK, each of whom play pivotal roles in maintaining energy balance and glucose homeostasis. Some are now the basis of several clinically used glucose-lowering and weight loss therapies. The environment in which these enteroendocrine cells exist is also complex, as they are exposed to numerous physiological inputs including ingested nutrients, circulating factors and metabolites produced from neighbouring gut microbiome. In this review, we examine the diverse means by which gut-derived hormones carry out their metabolic functions through their interactions with different metabolically important organs including the liver, pancreas, adipose tissue and brain. Furthermore, we discuss how nutrients and microbial metabolites affect gut hormone secretion and the mechanisms underlying these interactions.
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A Whole-Grain Diet Increases Glucose-Stimulated Insulin Secretion Independent of Gut Hormones in Adults at Risk for Type 2 Diabetes.
Malin, SK, Kullman, EL, Scelsi, AR, Godin, JP, Ross, AB, Kirwan, JP
Molecular nutrition & food research. 2019;(7):e1800967
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Abstract
INTRODUCTION The effect of whole-grain (WG) versus refined-grain (RG) diets on glucose-stimulated insulin secretion (GSIS) and β-cell function is unclear. METHODS In a double-blind crossover randomized controlled trial, 13 prediabetic adults (37.2 ± 1.8 y, BMI: 33.6 ± 1.4 kg m-2 , 2 h glucose: 146.9 ± 11.6 mg dL-1 ) are provided isocaloric-matched WG and RG diets for 8-weeks each, with an 8-10 week washout between diets. Glucose, insulin, and C-peptide are studied over 240 min following a 75 g OGTT. Incretins (GLP-1 and GIP), PYY, and total ghrelin are assessed at 0, 30, and 60 min. Mixed-meal diets for carbohydrate (54%), fat (28%), and protein (18%) contain either WG (50 g/1000 kcal) or equivalent RG. RESULTS Both diets induce fat loss (≈2 kg). While neither diet impacts early phase GSIS, the WG diet increases total GSIS (iAUC of C-peptide0-240 /Glc0-240 , p = 0.02) and β-cell function (disposition index; GSIS × insulin sensitivity, p = 0.02). GIP and PYY are unaltered by either diet, but GLP-1 is higher at 30 min following RG versus WG (p = 0.04). Ghrelin levels are higher at 60 min of the OGTT following both interventions (p = 0.01). CONCLUSION A WG-rich diet increases β-cell function independent of gut hormones in adults with prediabetes.
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Effect of physical exercise and training on gastrointestinal hormones in populations with different weight statuses.
Zouhal, H, Sellami, M, Saeidi, A, Slimani, M, Abbassi-Daloii, A, Khodamoradi, A, El Hage, R, Hackney, AC, Ben Abderrahman, A
Nutrition reviews. 2019;(7):455-477
Abstract
Several types of hormones exert control over appetite in humans. This narrative review explores the effects of exercise and training on the concentrations of gastrointestinal hormones in healthy and obese individuals. It focuses on the major hormones of appetite regulation: ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, leptin, and oxyntomodulin. In normal-weight and overweight individuals, responses to most of these hormones depend on the intensity of exercise and training. However, findings in obese individuals are limited in number and, to some degree, contradictory. Although some gastrointestinal hormones have been studied extensively (eg, leptin), most have not been investigated systematically. Further research is required to confirm the effectiveness of exercise and training on gut hormones and to better understand the effect of gut hormones on appetite and hunger suppression in individuals with obesity. Investigations to elucidate the impact of various forms of exercise that have recently engaged the public interest, eg, high-intensity interval training or concurrent aerobic and resistance training, are warranted.
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Effect of Meal Acceptability on Postprandial Appetite Scores and Hormones of Male Participants with Varied Adiposity.
El Helou, N, Obeid, OA, Olabi, A
Obesity (Silver Spring, Md.). 2019;(10):1627-1633
Abstract
OBJECTIVE This study portrays the effect of hedonic manipulation (high acceptability [HA] vs. low acceptability [LA]) on postprandial hormones and appetite scores in healthy males. METHODS Thirty participants (15 with normal weight and 15 with obesity) were recruited for a randomized, crossover design. They were randomly assigned to the HA or LA (with acesulfame-K) custard. Blood samples were drawn before the meals and for 4 hours after the meals and were analyzed for glucose, insulin, ghrelin, and glucagonlike peptide 1 (GLP-1). Appetite scores and subsequent energy intake were recorded. RESULTS Postprandial glucose, insulin, and ghrelin were different according to adiposity, whereas meal acceptability did not correspond to any significant difference in postprandial glucose, insulin, ghrelin, and GLP-1 concentrations. Appetite scores showed lower hunger, higher satiety, and fullness after the HA meal without a significant difference between the meals. Subsequent energy intake, expressed as a percentage of the resting energy expenditure, was higher in participants with obesity but did not reflect postprandial hormones and appetite scores; there was no significant difference between meals. CONCLUSIONS Hedonic properties and palatability do not affect gut hormones, mainly ghrelin and GLP-1. Moreover, their postprandial concentrations were not paralleled by similar changes in appetite scores, and both were not found to affect subsequent intake.
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Will medications that mimic gut hormones or target their receptors eventually replace bariatric surgery?
Kokkinos, A, Tsilingiris, D, le Roux, CW, Rubino, F, Mantzoros, CS
Metabolism: clinical and experimental. 2019;:153960
Abstract
Bariatric surgery is currently the most effective therapeutic modality through which sustained beneficial effects on weight loss and metabolic improvement are achieved. During recent years, indications for bariatric surgery have been expanded to include cases of poorly controlled type 2 (T2DM) diabetes mellitus in lesser extremes of body weight. A spectrum of the beneficial effects of surgery is attributed to robust changes of postprandial gut peptide responses that are observed post operatively. Consolidated knowledge regarding gut peptide physiology as well as emerging new evidence shedding light on the mode of action of previously overlooked gut hormones provide appealing potential obesity and T2DM therapeutic perspectives. The accumulation of evidence from the effect of exogenous administration of native gut peptides alone or in combinations to humans as well as the development of mimetic agents exerting agonistic effects on combinations of gut hormone receptors pave the way for future integrated gut peptide-based treatments, which may mimic the effects of bariatric surgery.
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Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity.
Dirksen, C, Graff, J, Fuglsang, S, Rehfeld, JF, Holst, JJ, Madsen, JL
American journal of physiology. Gastrointestinal and liver physiology. 2019;(3):G332-G337
Abstract
Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2 (range of 47.9-69.0)] and 10 men without obesity [BMI of 24.6 kg/m2 (range of 21.7-26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipid P = 0.046; GMETwater P = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion. NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.
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Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.
El-Salhy, M, Hatlebakk, JG, Hausken, T
Nutrients. 2019;(8)
Abstract
Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.
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Dose-Dependent Effects of Randomized Intraduodenal Whey-Protein Loads on Glucose, Gut Hormone, and Amino Acid Concentrations in Healthy Older and Younger Men.
Giezenaar, C, Luscombe-Marsh, ND, Hutchison, AT, Standfield, S, Feinle-Bisset, C, Horowitz, M, Chapman, I, Soenen, S
Nutrients. 2018;(1)
Abstract
Protein-rich supplements are used widely for the prevention and management of malnutrition in older people. We have reported that healthy older, compared to younger, adults have less suppression of energy intake by whey-protein-effects on appetite-related hormones are unknown. The objective was to determine the effects of intraduodenally administered whey-protein on glucose, gut hormone, and amino acid concentrations, and their relation to subsequent ad libitum energy intake at a buffet meal, in healthy older and younger men. Hydrolyzed whey-protein (30 kcal, 90 kcal, and 180 kcal) and a saline control (~0 kcal) were infused intraduodenally for 60 min in 10 younger (19-29 years, 73 ± 2 kg, 22 ± 1 kg/m²) and 10 older (68-81 years, 79 ± 2 kg, 26 ± 1 kg/m²) healthy men in a randomized, double-blind fashion. Plasma insulin, glucagon, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and amino acid concentrations, but not blood glucose, increased, while ghrelin decreased during the whey-protein infusions. Plasma GIP concentrations were greater in older than younger men. Energy intake correlated positively with plasma ghrelin and negatively with insulin, glucagon, GIP, GLP-1, PYY, and amino acids concentrations (p < 0.05). In conclusion, intraduodenal whey-protein infusions resulted in increased GIP and comparable ghrelin, insulin, glucagon, GIP, GLP-1, PYY, and amino acid responses in healthy older and younger men, which correlated to subsequent energy intake.
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Acute Effects of Dietary Carbohydrate Restriction on Glycemia, Lipemia and Appetite Regulating Hormones in Normal-Weight to Obese Subjects.
Samkani, A, Skytte, MJ, Thomsen, MN, Astrup, A, Deacon, CF, Holst, JJ, Madsbad, S, Rehfeld, JF, Krarup, T, Haugaard, SB
Nutrients. 2018;(9)
Abstract
Postprandial responses to food are highly dependent on the macronutrient composition of the diet. We investigated the acute effects of transition from the recommended moderately high carbohydrate (HC) diet towards a carbohydrate-reduced high-protein (CRHP) diet on postprandial glycemia, insulinemia, lipemia, and appetite-regulating hormones in non-diabetic adults. Fourteen subjects, including five males (Mean ± SD: age 62 ± 6.5; BMI 32 ± 7.6 kg/m²; hemoglobin A1c (HbA1c) 40 ± 3.0 mmol/mol; HOMA2-IR 2.1 ± 0.9) were included in this randomized, cross-over study. Iso-caloric diets were consumed for two consecutive days with a median wash-out period of 21 days (range 2⁻8 weeks) between diets (macronutrient energy composition: CRHP/HC; 31%/54% carbohydrate, 29%/16% protein, 40%/30% fat). Postprandial glucose, insulin secretion rate (ISR), triglycerides (TGs), non-esterified fatty acids (NEFAs), and satiety ratings were assessed after ingestion of breakfast (Br) and lunch (Lu), and gut hormones and glucagon were assessed after ingestion of Br. Compared with the HC diet, the CRHP diet reduced peak glucose concentrations (Br 11%, p = 0.024; Lu 11%, p < 0.001), glucose excursions (Br 80%, p = 0.20; Lu 85%, p < 0.001), and ISR (Br 31%; Lu 64%, both p < 0.001) whereas CRHP, as compared with HC, increased glucagon-like peptide-1 (Br 27%, p = 0.015) and glucagon values (Br 249%, p < 0.001). NEFA and TG levels increased in the CRHP diet as compared with the HC diet after Br, but no difference was found after Lu (NEFA Br 22%, p < 0.01; TG Br 42%, p = 0.012). Beta-cell glucose sensitivity, insulin clearance, cholecystokinin values, and subjective satiety ratings were unaffected. It is possible to achieve a reduction in postprandial glycemia and insulin without a deleterious effect on beta-cell glucose sensitivity by substituting part of dietary carbohydrate with iso-caloric protein and fat in subjects without type 2 diabetes mellitus (T2DM). The metabolic effects are more pronounced after the second meal.