scholarly journals Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation

2015 ◽  
Vol 4 ◽  
Author(s):  
Thomas Aranias ◽  
Alexandra Grosfeld ◽  
Christine Poitou ◽  
Amal Ait Omar ◽  
Maude Le Gall ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Density ◽  
Environmental Changes ◽  
Peptide Yy ◽  
High Fat ◽  
L Cell ◽  
Fat Consumption ◽  
Severely Obese ◽  
Obese Subjects ◽  
Glucagon Like Peptide 1

AbstractThe enterohormone glucagon-like peptide-1 (GLP-1) is required to amplify glucose-induced insulin secretion that facilitates peripheral glucose utilisation. Alteration in GLP-1 secretion during obesity has been reported but is still controversial. Due to the high adaptability of intestinal cells to environmental changes, we hypothesised that the density of GLP-1-producing cells could be modified by nutritional factors to prevent the deterioration of metabolic condition in obesity. We quantified L-cell density in jejunum samples collected during Roux-en-Y gastric bypass in forty-nine severely obese subjects analysed according to their fat consumption. In mice, we deciphered the mechanisms by which a high-fat diet (HFD) makes an impact on enteroendocrine cell density and function. L-cell density in the jejunum was higher in obese subjects consuming >30 % fat compared with low fat eaters. Mice fed a HFD for 8 weeks displayed an increase in GLP-1-positive cells in the jejunum and colon accordingly to GLP-1 secretion. The regulation by the HFD appears specific to GLP-1-producing cells, as the number of PYY (peptide YY)-positive cells remained unchanged. Moreover, genetically obese ob/ob mice did not show alteration of GLP-1-positive cell density in the jejunum or colon, suggesting that obesity per se is not sufficient to trigger the mechanism. The higher L-cell density in HFD-fed mice involved a rise in L-cell terminal differentiation as witnessed by the increased expression of transcription factors downstream of neurogenin3 (Ngn3). We suggest that the observed increase in GLP-1-positive cell density triggered by high fat consumption in humans and mice might favour insulin secretion and therefore constitute an adaptive response of the intestine to balance diet-induced insulin resistance.

scholarly journals GPR119 Regulates Murine Glucose Homeostasis Through Incretin Receptor-Dependent and Independent Mechanisms

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 374-383 ◽  
Author(s):  
Grace Flock ◽  
Dianne Holland ◽  
Yutaka Seino ◽  
Daniel J. Drucker
Keyword(s):  
Insulin Secretion ◽  
Gastric Emptying ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Peptide Yy ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Glucagon Like Peptide 1

Abstract G protein-coupled receptor 119 (GPR119) was originally identified as a β-cell receptor. However, GPR119 activation also promotes incretin secretion and enhances peptide YY action. We examined whether GPR119-dependent control of glucose homeostasis requires preservation of peptidergic pathways in vivo. Insulin secretion was assessed directly in islets, and glucoregulation was examined in wild-type (WT), single incretin receptor (IR) and dual IR knockout (DIRKO) mice. Experimental endpoints included plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY. Gastric emptying was assessed in WT, Glp1r−/−, DIRKO, Glp2r−/−, and GPR119−/− mice treated with the GPR119 agonist AR231453. AR231453 stimulated insulin secretion from WT and DIRKO islets in a glucose-dependent manner, improved glucose homeostasis, and augmented plasma levels of GLP-1, GIP, and insulin in WT and Gipr−/−mice. In contrast, although AR231453 increased levels of GLP-1, GIP, and insulin, it failed to lower glucose in Glp1r−/− and DIRKO mice. Furthermore, AR231453 did not improve ip glucose tolerance and had no effect on insulin action in WT and DIRKO mice. Acute GPR119 activation with AR231453 inhibited gastric emptying in Glp1r−/−, DIRKO, Glp2r−/−, and in WT mice independent of the Y2 receptor (Y2R); however, AR231453 did not control gastric emptying in GPR119−/− mice. Our findings demonstrate that GPR119 activation directly stimulates insulin secretion from islets in vitro, yet requires intact IR signaling and enteral glucose exposure for optimal control of glucose tolerance in vivo. In contrast, AR231453 inhibits gastric emptying independent of incretin, Y2R, or Glp2 receptors through GPR119-dependent pathways. Hence, GPR119 engages multiple complementary pathways for control of glucose homeostasis.

Colonic lactulose fermentation has no impact on glucagon-like peptide-1 and peptide-YY secretion in healthy young men

2021 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Simon Veedfald ◽  
Bolette Hartmann ◽  
Astrid Marie Gauguin ◽  
Søren Møller ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Young Men ◽  
Cell Secretion ◽  
L Cell ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Many ◽  
Peptide Secretion ◽  
The Impact

Abstract Context The colon houses most of our gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products. Objective To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state. Research Design and Methods Ten healthy young men were studied on three occasions after an overnight fast. On two study days, lactulose (20 g) was given orally, and compared to water intake on a third study day. For one of the lactulose visits participants underwent a full colonic evacuation. Over a six-hour study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen (H2), while gut peptide secretion, paracetamol and short chain fatty acid levels were measured in plasma. Results Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (p=0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting, and that fermentation and peptide secretion are not acutely related. Conclusion Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.

The effect of high-fat diets on gastric inhibitory polypeptide (gip) and insulin secretion in growing pigs

1990 ◽  
Vol 1990 ◽  
pp. 91-91
Author(s):  
A.A. Ponter ◽  
D.N. Salter ◽  
L.M. Morgan ◽  
P.R. Flatt
Keyword(s):  
Insulin Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Growing Pigs ◽  
High Fat ◽  
Enteroinsular Axis ◽  
Gut Hormone ◽  
High Fat Diets ◽  
Obese Subjects ◽  
Main Components ◽  
Fat Diets

Hyperinsulinaemia, which is associated with obesity and type II diabetes (Gama and Marks, 1989), may be due in part to an overactive enteroinsular axis. The gut hormone GIP is a potent stimulator of insulin secretion and is currently thought to be one of the main components of the enteroinsular axis. Exaggerated GIP responses have been observed after a mixed meal in obese subjects (Hampton, Kwasowski, Tan, Morgan and Marks, 1983), and a high-fat diet increases fat-stimulated GIP secretion in rats (Ebert, Willms, Brown and Creutzfeldt, 1976) and glucose stimulated GIP secretion in man (Morgan, Tredger, Hampton, Kwasowski, Wright, Dunn and Marks, 1983). This experiment was designed to investigate the effects of high-fat diets on the development of the biochemical parameters which are characteristic of obesity.

scholarly journals Glucagon-Like Peptide-1, Peptide YY, Hunger, and Satiety after Gastric Bypass Surgery in Morbidly Obese Subjects

2006 ◽  
Vol 91 (5) ◽  
pp. 1735-1740 ◽  
Author(s):  
Rosa Morínigo ◽  
Violeta Moizé ◽  
Melina Musri ◽  
Antonio M. Lacy ◽  
Salvador Navarro ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Bypass Surgery ◽  
Peptide Yy ◽  
Gastric Bypass Surgery ◽  
Morbidly Obese ◽  
Obese Subjects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals High-Fat Diet and Palmitate Alter the Rhythmic Secretion of Glucagon-Like Peptide-1 by the Rodent L-cell

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 586-599 ◽  
Author(s):  
Manuel Gil-Lozano ◽  
W. Kelly Wu ◽  
Alexandre Martchenko ◽  
Patricia L. Brubaker
Keyword(s):  
Molecular Clock ◽  
Rhythmic Activity ◽  
Induced Responses ◽  
High Fat ◽  
L Cells ◽  
L Cell ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Impact ◽  
High Sucrose

Abstract Secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is rhythmically regulated by an independent molecular clock. However, the impact of factors known to affect the activity of similar cell-autonomous clocks, such as circulating glucocorticoids and high-fat feeding, on GLP-1 secretory patterns remains to be elucidated. Herein the role of the endogenous corticosterone rhythm on the pattern of GLP-1 and insulin nutrient-induced responses was examined in corticosterone pellet-implanted rats. Moreover, the impact of nutrient excess on the time-dependent secretion of both hormones was assessed in rats fed a high-fat, high-sucrose diet. Finally, the effects of the saturated fatty acid, palmitate, on the L-cell molecular clock and GLP-1 secretion were investigated in vitro using murine GLUTag L-cells. Diurnal variations in GLP-1 and insulin nutrient-induced responses were maintained in animals lacking an endogenous corticosterone rhythm, suggesting that glucocorticoids are not the predominant entrainment factor for L-cell rhythmic activity. In addition to hyperglycemia, hyperinsulinemia, insulin resistance, and disorganization of feeding behavior, high-fat high-sucrose-fed rats showed a total abrogation of the diurnal variation in GLP-1 and insulin nutrient-induced responses, with comparable levels of both hormones at the normal peak (5:00 pm) and trough (5:00 am) of their daily pattern. Finally, palmitate incubation induced profound derangements in the rhythmic expression of circadian oscillators in GLUTag L-cells and severely impaired the secretory activity of these cells. Collectively our findings demonstrate that obesogenic diets disrupt the rhythmic activity of the L-cell, partially through a direct effect of specific nutritional components.

scholarly journals Ileal microbial shifts after Roux-en-Y gastric bypass orchestrate changes in glucose metabolism through modulation of bile acids and L-cell adaptation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jerry T. Dang ◽  
Valentin Mocanu ◽  
Heekuk Park ◽  
Michael Laffin ◽  
Caroline Tran ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Glucose Tolerance ◽  
Bile Acids ◽  
Cell Density ◽  
Glucose Homeostasis ◽  
Alpha Diversity ◽  
Microbial Composition ◽  
L Cells ◽  
L Cell ◽  
Glucagon Like Peptide 1

AbstractRoux-en-Y gastric bypass (RYGB)-induced glycemic improvement is associated with increases in glucagon-like-peptide-1 (GLP-1) secreted from ileal L-cells. We analyzed changes in ileal bile acids and ileal microbial composition in diet-induced-obesity rats after RYGB or sham surgery to elucidate the early and late effects on L-cells and glucose homeostasis. In early cohorts, there were no significant changes in L-cell density, GLP-1 or glucose tolerance. In late cohorts, RYGB demonstrated less weight regain, improved glucose tolerance, increased L-cell density, and increased villi height. No difference in the expression of GLP-1 genes was observed. There were lower concentrations of ileal bile acids in the late RYGB cohort. Microbial analysis demonstrated decreased alpha diversity in early RYGB cohorts which normalized in the late group. The early RYGB cohorts had higher abundances of Escherichia–Shigella but lower abundances of Lactobacillus, Adlercreutzia, and Proteus while the late cohorts demonstrated higher abundances of Escherichia–Shigella and lower abundances of Lactobacillus. Shifts in Lactobacillus and Escherichia–Shigella correlated with decreases in multiple conjugated bile acids. In conclusion, RYGB caused a late and substantial increase in L-cell quantity with associated changes in bile acids which correlated to shifts in Escherichia–Shigella and Lactobacillus. This proliferation of L-cells contributed to improved glucose homeostasis.

scholarly journals Whey Proteins Reduce Appetite, Stimulate Anorexigenic Gastrointestinal Peptides and Improve Glucometabolic Homeostasis in Young Obese Women

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 247 ◽  
Author(s):  
Antonello E. Rigamonti ◽  
Roberto Leoncini ◽  
Claudia Casnici ◽  
Ornella Marelli ◽  
Alessandra De Col ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Whey Proteins ◽  
Fixed Dose ◽  
Obese Women ◽  
Mixed Meal ◽  
Control Blood Glucose ◽  
Gastrointestinal Peptides ◽  
Obese Subjects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Proteins, particularly whey proteins, represent the most satiating macronutrient in animals and humans. A dietetic regimen based on proteins enriched preload before eating might be a strategy to counteract obesity. Aims and Methods: The aim of the present study was to evaluate the effects of an isocaloric drink containing whey proteins or maltodextrins (preload) on appetite (satiety/hunger measured by a visual analogue scale or VAS), glucometabolic control (blood glucose/insulin), and anorexigenic gastrointestinal peptides (pancreatic polypeptide or PP, glucagon-like peptide 1 or GLP-1 and peptide YY or PYY) in a cohort of obese young women (n = 9; age: 18.1 ± 3.0 years; body mass index, BMI: 38.8 ± 4.5 kg/m2). After two and a half hours, they were administered with a mixed meal at a fixed dose; satiety and hunger were measured by VAS. Results: Each drink significantly augmented satiety and reduced hunger, and the effects were more evident with whey proteins than maltodextrins. Similarly, there were significant increases in GLP-1 and PYY levels (but not PP) after the ingestion of each drink; these anorexigenic responses were higher with whey proteins than maltodextrins. While insulinemia identically increased after each drink, whey proteins induced a lower glycemic response than maltodextrins. No differences in satiety and hunger were found after the meal, which is presumably due to the late administration of the meal test, when the hypophagic effect of whey proteins was disappearing. Conclusions: While whey proteins actually reduce appetite, stimulate anorexigenic gastrointestinal peptides, and improve glucometabolic homeostasis in young obese women, further additional studies are mandatory to demonstrate their hypophagic effects in obese subjects, when administered as preload before eating.

scholarly journals A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota–Gut–Brain Axis in Satiety Regulation

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 632
Author(s):  
Nuria A. Pizarroso ◽  
Pablo Fuciños ◽  
Catarina Gonçalves ◽  
Lorenzo Pastrana ◽  
Isabel R. Amado
Keyword(s):  
Metabolic Diseases ◽  
Environmental Changes ◽  
Peptide Yy ◽  
Brain Regions ◽  
Nutrient Sensing ◽  
Bioactive Molecules ◽  
Intestinal Hormones ◽  
Signaling Systems ◽  
Chip Technology ◽  
Glucagon Like Peptide 1

Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.

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