scholarly journals Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7–36) Amide or Exendin-(9–39) Alters Body Weight in the Rat**This work was supported by the United Kingdom Medical Research Council.

Endocrinology ◽  
1999 ◽  
Vol 140 (1) ◽  
pp. 244-250 ◽  
Author(s):  
Karim Meeran ◽  
Donal O’Shea ◽  
C. Mark B. Edwards ◽  
Mandy D. Turton ◽  
Melanie M. Heath ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Research Council ◽  
Medical Research Council ◽  
Reduce Food Intake ◽  
The United Kingdom ◽  
Ad Libitum ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Central nervous system glucagon-like peptide-1-(7–36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (icv) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9–39), affects food intake and body weight. Daily icv injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 ± 5 g (P < 0.02 compared with saline-injected controls). Daily icv administration of 30 nmol exendin-(9–39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 ± 2 g (P < 0.02 compared with saline-injected controls). Twice daily icv injections of 30 nmol exendin-(9–39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 ± 4 g compared with 14 ± 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to icv GLP-1 or exendin-(9–39). GLP-1 may thus be involved in the regulation of body weight in the rat.

scholarly journals Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents

FEBS Letters ◽  
1997 ◽  
Vol 415 (2) ◽  
pp. 134-138 ◽  
Author(s):  
Anthony P. Goldstone ◽  
Julian G. Mercer ◽  
Irene Gunn ◽  
Kim M. Moar ◽  
C.Mark B. Edwards ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Reduce Food Intake ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives

2002 ◽  
Vol 440 (2-3) ◽  
pp. 269-279 ◽  
Author(s):  
Juris J. Meier ◽  
Baptist Gallwitz ◽  
Wolfgang E. Schmidt ◽  
Michael A. Nauck
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

2013 ◽  
Vol 221 (1) ◽  
pp. T1-T16 ◽  
Author(s):  
L van Bloemendaal ◽  
J S ten Kulve ◽  
S E la Fleur ◽  
R G Ijzerman ◽  
M Diamant
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Physiological Role ◽  
Brain Regions ◽  
Gastric Distension ◽  
Cns Activity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The delivery of nutrients to the gastrointestinal tract after food ingestion activates the secretion of several gut-derived mediators, including the incretin hormone glucagon-like peptide 1 (GLP-1). GLP-1 receptor agonists (GLP-1RA), such as exenatide and liraglutide, are currently employed successfully in the treatment of patients with type 2 diabetes mellitus. GLP-1RA improve glycaemic control and stimulate satiety, leading to reductions in food intake and body weight. Besides gastric distension and peripheral vagal nerve activation, GLP-1RA induce satiety by influencing brain regions involved in the regulation of feeding, and several routes of action have been proposed. This review summarises the evidence for a physiological role of GLP-1 in the central regulation of feeding behaviour and the different routes of action involved. Also, we provide an overview of presently available data on pharmacological stimulation of GLP-1 pathways leading to alterations in CNS activity, reductions in food intake and weight loss.

scholarly journals Peripheral and Central GLP-1 Receptor Populations Mediate the Anorectic Effects of Peripherally Administered GLP-1 Receptor Agonists, Liraglutide and Exendin-4

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3103-3112 ◽  
Author(s):  
Scott E. Kanoski ◽  
Samantha M. Fortin ◽  
Myrtha Arnold ◽  
Harvey J. Grill ◽  
Matthew R. Hayes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
Vagal Afferents ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Higher Doses ◽  
Cns Delivery

The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists, exendin-4 and liraglutide, suppress food intake and body weight. The mediating site(s) of action for the anorectic effects produced by peripheral administration of these GLP-1R agonists are not known. Experiments addressed whether food intake suppression after ip delivery of exendin-4 and liraglutide is mediated exclusively by peripheral GLP-1R or also involves direct central nervous system (CNS) GLP-1R activation. Results showed that CNS delivery [third intracerebroventricular (3rd ICV)] of the GLP-1R antagonist exendin-(9–39) (100 μg), attenuated the intake suppression by ip liraglutide (10 μg) and exendin-4 (3 μg), particularly at 6 h and 24 h. Control experiments show that these findings appear to be based neither on the GLP-1R antagonist acting as a nonspecific competing orexigenic signal nor on blockade of peripheral GLP-1R via efflux of exendin-(9–39) to the periphery. To assess the contribution of GLP-1R expressed on subdiaphragmatic vagal afferents to the anorectic effects of liraglutide and exendin-4, food intake was compared in rats with complete subdiaphragmatic vagal deafferentation and surgical controls after ip delivery of the agonists. Both liraglutide and exendin-4 suppressed food intake at 3 h, 6 h, and 24 h for controls; for subdiaphragmatic vagal deafferentation rats higher doses of the GLP-1R agonists were needed for significant food intake suppression, which was observed at 6 h and 24 h after liraglutide and at 24 h after exendin-4. Conclusion: Food intake suppression after peripheral administration of exendin-4 and liraglutide is mediated by activation of GLP-1R expressed on vagal afferents as well as direct CNS GLP-1R activation.

scholarly journals Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6

2013 ◽  
Vol 110 (40) ◽  
pp. 16199-16204 ◽  
Author(s):  
R. Shirazi ◽  
V. Palsdottir ◽  
J. Collander ◽  
F. Anesten ◽  
H. Vogel ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Suppression of Food Intake by Glucagon-Like Peptide-1 Receptor Agonists: Relative Potencies and Role of Dipeptidyl Peptidase-4

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 5735-5745 ◽  
Author(s):  
Lene Jessen ◽  
Benedikt A. Aulinger ◽  
Jonathan L. Hassel ◽  
Kyle J. Roy ◽  
Eric P. Smith ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Food Intake ◽  
Dipeptidyl Peptidase ◽  
Reduce Food Intake ◽  
Wild Type ◽  
Dipeptidyl Peptidase 4 ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
High Doses

Abstract Administration of the glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1 and exendin-4 (Ex-4) directly into the central nervous system decreases food intake. But although Ex-4 potently suppresses food intake after peripheral administration, the effects of parenteral GLP-1 are variable and not as strong. A plausible explanation for these effects is the rapid inactivation of circulating GLP-1 by dipeptidyl peptidase-4 (DPP-4), an enzyme that does not alter Ex-4 activity. To test this hypothesis, we assessed the relative potency of Ex-4 and GLP-1 under conditions in which DPP-4 activity was reduced. Outbred rats, wild-type mice, and mice with a targeted deletion of DPP-4 (Dpp4−/−) were treated with GLP-1 alone or in combination with the DPP-4 inhibitor vildagliptin, Ex-4, or saline, and food intake was measured. GLP-1 alone, even at high doses, did not affect feeding in wild-type mice or rats but did reduce food intake when combined with vildagliptin or given to Dpp4−/− mice. Despite plasma clearance similar to DPP-4-protected GLP-1, equimolar Ex-4 caused greater anorexia than vildagliptin plus GLP-1. To determine whether supraphysiological levels of endogenous GLP-1 would suppress food intake if protected from DPP-4, rats with Roux-en-Y gastric bypass and significantly elevated postprandial plasma GLP-1 received vildagliptin or saline. Despite 5-fold greater postprandial GLP-1 in these animals, vildagliptin did not affect food intake in Roux-en-Y gastric bypass rats. Thus, in both mice and rats, peripheral GLP-1 reduces food intake significantly less than Ex-4, even when protected from DPP-4. These findings suggest distinct potencies of GLP-1 receptor agonists on food intake that cannot be explained by plasma pharmacokinetics.

scholarly journals Modulation of Food Intake by Differential TAS2R Stimulation in Rat

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3784
Author(s):  
Carme Grau-Bové ◽  
Alba Miguéns-Gómez ◽  
Carlos González-Quilen ◽  
José-Antonio Fernández-López ◽  
Xavier Remesar ◽  
...  
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Reduce Food Intake ◽  
Intestinal Segments ◽  
Regulate Food Intake ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Specific Stimulation ◽  
Ghrelin Secretion ◽  
Stimulation Of

Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize that optimal stimulation of TAS2Rs could help to modulate enteroendocrine secretions and thus regulate food intake. To determine this, we have assayed the response to specific agonists for hTAS2R5, hTAS2R14 and hTAS2R39 on enteroendocrine secretions from intestinal segments and food intake in rats. We found that hTAS2R5 agonists stimulate glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK), and reduce food intake. hTAS2R14 agonists induce GLP1, while hTASR39 agonists tend to increase peptide YY (PYY) but fail to reduce food intake. The effect of simultaneously activating several receptors is heterogeneous depending on the relative affinity of the agonists for each receptor. Although detailed mechanisms are not clear, bitter compounds can stimulate differentially enteroendocrine secretions that modulate food intake in rats.

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist, Exendin-4, Regulates Feeding-Associated Neuropeptides in Hypothalamic Neurons in Vivo and in Vitro

Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2208-2222 ◽  
Author(s):  
Prasad S. Dalvi ◽  
Anaies Nazarians-Armavil ◽  
Matthew J. Purser ◽  
Denise D. Belsham
Keyword(s):  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Arcuate Nucleus ◽  
Neuronal Cell ◽  
Reduce Food Intake ◽  
Hypothalamic Neurons ◽  
Melanocyte Stimulating Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Stimulating Hormone

Exendin-4, a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist, is a potential regulator of feeding behavior through its ability to inhibit gastric emptying, reduce food intake, and induce satiety. GLP-1R activation by exendin-4 induces anorexia; however, the specific populations of neuropeptidergic neurons activated by exendin-4 within the hypothalamus, the central regulator of energy homeostasis, remain unclear. This study determines whether exendin-4 regulates hypothalamic neuropeptide expression and explores the signaling mechanisms involved. The distribution and quantity of exendin-4-induced c-Fos immunoreactivity were evaluated to determine activation of α-melanocyte-stimulating hormone/proopiomelanocortin, neuropeptide Y, neurotensin (NT), and ghrelin neurons in hypothalamic nuclei during exendin-4-induced anorexia in mice. Additionally, exendin-4 action on NT and ghrelin transcript regulation was examined in immortalized hypothalamic neurons. With anorexia induced by intracerebroventricular exendin-4, α-melanocyte-stimulating hormone/proopiomelanocortin and neuropeptide Y neurons were activated in the arcuate nucleus, with simultaneous activation of NT-expressing neurons in the paraventricular nucleus, and ghrelin-expressing neurons in the arcuate nucleus, paraventricular nucleus, and periventricular hypothalamus, suggesting that neurons in one or more of these areas mediate the anorexic action of exendin-4. In the hypothalamic neuronal cell models, exendin-4 increased cAMP, cAMP response element-binding protein/activating transcription factor-1 and c-Fos activation, and via a protein kinase A-dependent mechanism regulated NT and ghrelin mRNA expression, indicating that these neuropeptides may serve as downstream mediators of exendin-4 action. These findings provide a previously unrecognized link between central GLP-1R activation by exendin-4 and the regulation of hypothalamic NT and ghrelin. Further understanding of this central GLP-1R activation may lead to safe and effective therapeutics for the treatment of metabolic disorders.

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