Changes in Satiety Hormones in Response to Leptin Treatment in a Patient with Leptin Deficiency

2018 ◽  
Vol 90 (6) ◽  
pp. 424-430 ◽  
Author(s):  
Christian L. Roth ◽  
Julia von Schnurbein ◽  
Clinton Elfers ◽  
Anja Moss ◽  
Martin Wabitsch
Keyword(s):  
Energy Homeostasis ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Calorie Intake ◽  
Strong Increase ◽  
Morbidly Obese ◽  
Gut Peptides ◽  
Treatment Results ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: We tested whether leptin treatment affects secretion of satiety-related gut peptides and brain-derived neurotrophic factor (BDNF), which is a regulator of energy homeostasis downstream of hypothalamic leptin signaling. Methods: We report the case of a morbidly obese 14.7-year-old girl with a novel previously reported homozygous leptin gene mutation, in whom hormone secretion was evaluated in 30-min intervals for 10 h (07.30–17.30) to assess BDNF, insulin, glucagon-like peptide-1 (GLP-1), ghrelin, and peptide YY (PYY) secretion before as well as 11 and 46 weeks after start of metreleptin treatment. Results: Leptin substitution resulted in strong reductions of body fat and calorie intake. Insulin secretion increased by 58.9% after 11 weeks, but was reduced by –44.8% after 46 weeks compared to baseline. Similarly, GLP-1 increased after 11 weeks (+15.2%) and decreased after 46 weeks. PYY increased consistently (+5%/ +13.2%, after 11/46 weeks). Ghrelin decreased after 46 weeks (–11%). BDNF secretion was not affected by leptin treatment. Conclusion: The strong increase in insulin and GLP-1 secretion after 11 weeks of metreleptin treatment cannot be explained by reduced adiposity and might contribute to improved central satiety. Observed changes of PYY can lead to increased satiety as well. However, leptin replacement does not seem to affect circulating BDNF levels.

scholarly journals Regulation of Appetite and Satiety by Gastrointestinal Peptides

2021 ◽  
Vol 30 (1) ◽  
pp. 14-21
Author(s):  
Sarah H. Mhaibes ◽  
Najwan K. Fakree ◽  
Sonia I. Naser
Keyword(s):  
Food Consumption ◽  
Energy Homeostasis ◽  
Peptide Yy ◽  
Brain Regions ◽  
Gut Peptides ◽  
Major Health Problem ◽  
Vital Functions ◽  
Gastrointestinal Peptides ◽  
Glucagon Like Peptide 1 ◽  
The Brain

In recent decades, global obesity has increased significantly, causing a major health problem with associated complications and major socioeconomic issues. The central nervous system (CNS), particularly the hypothalamus, regulates food intake through sensing the metabolic signals of peripheral organs and modulating feeding behaviors.  The hypothalamus interacts with other brain regions such as the brain stem to perform these vital functions. The gut plays a crucial role in controlling food consumption and energy homeostasis. The gut releases orexigenic and anorexigenic hormones that interact directly with the CNS or indirectly through vagal afferent neurons. Gastrointestinal peptides (GIP) including cholecystokinin, peptide YY, Nesfatin-1, glucagon-like peptide 1, and oxyntomodulin send satiety signals to the brain and ghrelin transmit hunger signals to the brain. The GIP is essential for the control of food consumption; thus, explain the link between the gastrointestinal tract (GIT) and the brain is important for managing obesity and its associated diseases. This review aimed to explain the role of gut peptides in satiety and hunger control.

scholarly journals Ghrelin Stimulates Gastric Emptying and Hunger in Normal-Weight Humans

2006 ◽  
Vol 91 (9) ◽  
pp. 3296-3302 ◽  
Author(s):  
F. Levin ◽  
T. Edholm ◽  
P. T. Schmidt ◽  
P. Grybäck ◽  
H. Jacobsson ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Normal Weight ◽  
Lag Phase ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
Ghrelin Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. Main Objective: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. Design: This was a randomized, double-blind, crossover study. Subjects: Subjects included normal human volunteers and patients with GH deficiency. Intervention: Intervention included saline or ghrelin (10 pmol/kg·min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. Main Outcome Measures: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. Results: The emptying rate was significantly faster for ghrelin (1.26 ± 0.1% per minute), compared with saline (0.83% per minute) (P < 0.001). The lag phase (16.2 ± 2.2 and 26.5 ± 3.8 min) and half-emptying time (49.4 ± 3.9 and 75.6 ± 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P < 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. Conclusion: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.

scholarly journals Nutrient sensing and signalling by the gut

2012 ◽  
Vol 71 (4) ◽  
pp. 446-455 ◽  
Author(s):  
Rojo Rasoamanana ◽  
Nicolas Darcel ◽  
Gilles Fromentin ◽  
Daniel Tomé
Keyword(s):  
Peptide Yy ◽  
Nutrient Sensing ◽  
Vagal Afferents ◽  
Adaptive Responses ◽  
Gut Peptides ◽  
Intestinal Peptides ◽  
Nutrient Transporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Recent advances highlight that nutrient receptors (such as T1R1/T1R3 heterodimer, Ca sensing receptor and GPR93 for amino acids and protein, GPR40, GPR41, GPR43 and GPR120 for fatty acids, T1R2/T1R3 heterodimer for monosaccharides) are expressed in the apical face of the gut and sense nutrients in the lumen. They transduce signals for the regulation of nutrient transporter expressions in the apical face. Interestingly, they are also localised in enteroendocrine cells (EEC) and mainly exert a direct control on the secretion in the lamina propria of gastro-intestinal peptides such as cholecystokinin, glucagon-like peptide-1 and peptide YY in response to energy nutrient transit and absorption in the gut. This informs central nuclei involved in the control of feeding such as the hypothalamus and nucleus of the solitary tract of the availability of these nutrients and thus triggers adaptive responses to maintain energy homoeostasis. These nutrient receptors then have a prominent position since they manage nutrient absorption and are principally the generator of the first signal of satiation mechanisms mainly transmitted to the brain by vagal afferents. Moreover, tastants are also able to elicit gut peptides secretion via chemosensory receptors expressed in EEC. Targeting these nutrient and tastant receptors in EEC may thus be helpful to promote satiation and so to fight overfeeding and its consequences.

Peptide YY and Glucagon-like Peptide-1 in Morbidly Obese Patients Before and After Surgically Induced Weight Loss

2007 ◽  
Vol 17 (12) ◽  
pp. 1571-1577 ◽  
Author(s):  
Thomas Reinehr ◽  
Christian L. Roth ◽  
Gerit-Holger Schernthaner ◽  
Hans-Peter Kopp ◽  
Stefan Kriwanek ◽  
...  
Keyword(s):  
Weight Loss ◽  
Peptide Yy ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Before And After ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Surgically Induced

scholarly journals Current and emerging concepts on the role of peripheral signals in the control of food intake and development of obesity

2012 ◽  
Vol 108 (5) ◽  
pp. 778-793 ◽  
Author(s):  
F. A. Duca ◽  
M. Covasa
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Peptide Yy ◽  
Body Weight Gain ◽  
Gut Peptides ◽  
Gastrointestinal Peptides ◽  
Term Energy ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity

The gastrointestinal peptides are classically known as short-term signals, primarily inducing satiation and/or satiety. However, accumulating evidence has broadened this view, and their role in long-term energy homeostasis and the development of obesity has been increasingly recognised. In the present review, the recent research involving the role of satiation signals, especially ghrelin, cholecystokinin, glucagon-like peptide 1 and peptide YY, in the development and treatment of obesity will be discussed. Their activity, interactions and release profile vary constantly with changes in dietary and energy influences, intestinal luminal environment, body weight and metabolic status. Manipulation of gut peptides and nutrient sensors in the oral and postoral compartments through diet and/or changes in gut microflora or using multi-hormone ‘cocktail’ therapy are among promising approaches aimed at reducing excess food consumption and body-weight gain.

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 Minireview: Gut Peptides Regulating Satiety

Endocrinology ◽  
2004 ◽  
Vol 145 (6) ◽  
pp. 2660-2665 ◽  
Author(s):  
Maralyn R. Druce ◽  
Caroline J. Small ◽  
Stephen R. Bloom
Keyword(s):  
Body Weight ◽  
Gastrointestinal Tract ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Premature Death ◽  
Gut Peptides ◽  
The United Kingdom ◽  
Glucagon Like Peptide ◽  
Low Levels ◽  
Glucagon Like Peptide 1

Abstract The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appetite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in humans and rodents. Obesity is the current major cause of premature death in the United Kingdom, killing almost 1000 people per week. Worldwide, its prevalence is accelerating. There is currently no effective answer to the pandemic of obesity, but replacement of the low levels of peptide YY observed in the obese may represent an effective antiobesity therapy.

scholarly journals Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

2019 ◽  
Vol 316 (5) ◽  
pp. G574-G584 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Samuel Addison Jack Trammell ◽  
Nicolai Jacob Wewer Albrechtsen ◽  
Kristina Schoonjans ◽  
Reidar Albrechtsen ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Peptide Yy ◽  
Whole Body ◽  
Rat Colon ◽  
G Protein Coupled Receptor ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion.NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.

scholarly journals Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway

2000 ◽  
Vol 279 (5) ◽  
pp. G925-G930 ◽  
Author(s):  
G. Cuche ◽  
J. C. Cuber ◽  
C. H. Malbert
Keyword(s):  
Gastric Motility ◽  
Short Chain Fatty Acid ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Maximal Amplitude ◽  
Inhibiting Factor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 ± 1.2 vs. 49 ± 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 ± 0.11 vs. 1.3 ± 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 ± 1.0 and 34 ± 0.8 vs. 47 ± 1.3 and 43 ± 1.2%; frequency, 1.4 ± 0.07 and 1.6 ± 0.06 vs. 1.1 ± 0.14 and 1.0 ± 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

scholarly journals The endocrine effects of bitter tastant administration in the gastrointestinal system - Intragastric versus intraduodenal administration

2021 ◽  
Author(s):  
Wout Verbeure ◽  
Eveline Deloose ◽  
Joran Tóth ◽  
Jens F. Rehfeld ◽  
Lukas Van Oudenhove ◽  
...  
Keyword(s):  
Feeding Tube ◽  
Gut Peptides ◽  
Nasogastric Feeding ◽  
Physiological Relevance ◽  
Quinine Hydrochloride ◽  
Healthy Female ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Acyl Ghrelin ◽  
Intraduodenal Administration

Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill". However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1) the site of administration: intragastrically (IG) or intraduodenally (ID), 2) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1µmol/kg), QHCl (10µmol/kg) or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min prior to administration and every 10 min after administration for a period of 2 hours. Hunger was rated at the same timepoints on a visual analogue scale (VAS). ID bitter administration did not affect hunger sensations, motilin or acyl-ghrelin release compared with its PLC infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50-70 minutes after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 minutes before food intake.

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