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.

Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery

2016 ◽  
Vol 40 (11) ◽  
pp. 1699-1706 ◽  
Author(s):  
M S Svane ◽  
N B Jørgensen ◽  
K N Bojsen-Møller ◽  
C Dirksen ◽  
S Nielsen ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Food Intake ◽  
Bypass Surgery ◽  
Peptide Yy ◽  
Gastric Bypass Surgery ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

2015 ◽  
Vol 309 (10) ◽  
pp. G816-G825 ◽  
Author(s):  
John P. Vu ◽  
Deepinder Goyal ◽  
Leon Luong ◽  
Suwan Oh ◽  
Ravneet Sandhu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Peptide Yy ◽  
Dark Phase ◽  
Dependent Manner ◽  
Pac1 Receptor ◽  
Intraperitoneal Treatment ◽  
Regulate Food Intake ◽  
Feeding Parameters ◽  
Glucagon Like Peptide 1

Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system, where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1-deficient (PAC1−/−) and age-matched wild-type (WT) mice intraperitoneally injected with PACAP1–38 or PACAP1–27 before the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY, pancreatic polypeptide, and insulin were measured following PACAP1–38 administration in fasted WT mice. PACAP1–38/PACAP1–27 injected into WT mice significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP1–38 injected into PAC1−/− mice failed to significantly change food intake. Importantly, PACAP1–38 reduced plasma levels of active ghrelin compared with vehicle in WT mice. In PAC1−/− mice, fasting levels of active ghrelin, GLP-1, insulin, and leptin and postprandial levels of active ghrelin and insulin were significantly altered compared with levels in WT mice. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP1–38/PACAP1–27 significantly reduced appetite and food intake through PAC1. In PAC1−/− mice, the regulation of anorexigenic/orexigenic hormones was abolished, whereas active ghrelin remained elevated even postprandially. PACAP significantly reduced active ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment.

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.

Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity

2005 ◽  
Vol 289 (3) ◽  
pp. R729-R737 ◽  
Author(s):  
Karine Proulx ◽  
Daniela Cota ◽  
Tamara R. Castañeda ◽  
Matthias H. Tschöp ◽  
David A. D'Alessio ◽  
...  
Keyword(s):  
Food Intake ◽  
Motor Activity ◽  
Peptide Yy ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein A ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Induced Changes

Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-α. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Because the anorexigenic effect of OEA is associated with delayed feeding onset and reduced locomotion, we examined whether intraperitoneal administration of OEA results in nonspecific behavioral effects that contribute to the anorexia in rats. Moreover, we determined whether circulating levels of other gut hormones are modulated by OEA and whether CCK is involved in OEA-induced anorexia. Our results indicate that OEA reduces food intake without causing a conditioned taste aversion or reducing sodium appetite. It also failed to induce a conditioned place aversion. However, OEA induced changes in posture and reduced spontaneous activity in the open field. This likely underlies the reduced heat expenditure and sodium consumption observed after OEA injection, which disappeared within 1 h. The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-α agonist Wy-14643. Plasma levels of ghrelin, peptide YY, glucagon-like peptide 1, and apolipoprotein A-IV were not changed by OEA. Finally, antagonism of CCK-1 receptors did not affect OEA-induced anorexia. These results suggest that OEA suppresses feeding without causing visceral illness and that neither ghrelin, peptide YY, glucagon-like peptide 1, apolipoprotein A-IV, nor CCK plays a critical role in this effect. Despite that OEA-induced anorexia is unlikely to be due to impaired motor activity, our data raise a cautionary note in how specific behavioral and metabolic effects of OEA should be interpreted.

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.

Fat digestion is required for suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid

2005 ◽  
Vol 289 (6) ◽  
pp. E948-E953 ◽  
Author(s):  
Christine Feinle-Bisset ◽  
Michael Patterson ◽  
Mohammad A. Ghatei ◽  
Stephen R. Bloom ◽  
Michael Horowitz
Keyword(s):  
Pancreatic Polypeptide ◽  
Peptide Yy ◽  
Young Males ◽  
Healthy Humans ◽  
Fat Digestion ◽  
Fat Infusion ◽  
Glucagon Like Peptide 1 ◽  
Induced Changes ◽  
Ghrelin Secretion ◽  
Stimulation Of

Stimulation of cholecystokinin and glucagon-like peptide-1 secretion by fat is mediated by the products of fat digestion. Ghrelin, peptide YY (PYY), and pancreatic polypeptide (PP) appear to play an important role in appetite regulation, and their release is modulated by food ingestion, including fat. It is unknown whether fat digestion is a prerequisite for their suppression (ghrelin) or release (PYY, PP). Moreover, it is not known whether small intestinal exposure to fat is sufficient to suppress ghrelin secretion. Our study aimed to resolve these issues. Sixteen healthy young males received, on two separate occasions, 120-min intraduodenal infusions of a long-chain triglyceride emulsion (2.8 kcal/min) 1) without (condition FAT) or 2) with (FAT-THL) 120 mg of tetrahydrolipstatin (THL, lipase inhibitor), followed by a standard buffet-style meal. Blood samples for ghrelin, PYY, and PP were taken throughout. FAT infusion was associated with a marked, and progressive, suppression of plasma ghrelin from t = 60 min ( P < 0.001) and stimulation of PYY from t = 30 min ( P < 0.01). FAT infusion also stimulated plasma PP (P ≤ 0.01), and the release was immediate. FAT-THL completely abolished the FAT-induced changes in ghrelin, PYY, and PP. In response to the meal, plasma ghrelin was further suppressed, and PYY and PP stimulated, during both FAT and FAT-THL infusions. In conclusion, in healthy humans, 1) the presence of fat in the small intestine suppresses ghrelin secretion, and 2) fat-induced suppression of ghrelin and stimulation of PYY and PP is dependent on fat digestion.

scholarly journals The Glucagon-Like Peptide 1 Receptor Agonist Liraglutide Stimulates Mechanistic Target of Rapamycin (mTOR) Signaling via PKA And Akt

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A510-A511
Author(s):  
Thao D V Le ◽  
Dianxin Liu ◽  
Sheila Collins ◽  
Julio E Ayala
Keyword(s):  
Food Intake ◽  
Cho Cells ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Mechanistic Target Of Rapamycin ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Pre Treatment ◽  
Mtor Activity ◽  
Stimulation Of

Abstract Glucagon-like peptide 1 receptor (GLP-1R) agonists enhance glucose-stimulated insulin secretion and act on several regions of the brain to reduce food intake and body weight, making the GLP-1R a major therapeutic target for the treatment of type 2 diabetes and obesity. Surprisingly, little is known about the signaling mechanisms mediating the food intake-lowering effects of GLP-1R agonists. We have previously shown that inhibiting the mechanistic Target of Rapamycin (mTOR) in the ventromedial hypothalamus blocks anorexia induced by GLP-1R activation in this brain nucleus (1). Therefore, the goal of the present studies is to elucidate the mechanisms by which GLP-1R activation stimulates mTOR signaling. To accomplish this, we treated Chinese Hamster Ovary cells stably expressing the human GLP-1R with the GLP-1R agonist liraglutide (Lira) in combination with inhibitors of various signaling molecules. Since PKA is a canonical target of GLP-1R signaling, and PKA phosphorylates mTOR and its regulating protein Raptor following β-adrenergic stimulation (2), we used the PKA inhibitors H89 and KT 5720 to examine whether PKA is required for the stimulation of mTOR activity by Lira. We expressed myc-tagged mTOR or Raptor in GLP-1R stably expressing CHO cells, treated them with Lira, immunoprecipitated myc-mTOR or myc-Raptor, and immunoblotted for the PKA substrate RRXS/T motif. We found that Lira significantly increased PKA-substrate motif phosphorylation of myc-Raptor but not myc-mTOR, and this was blocked by pre-treatment with H89. Lira also failed to stimulate phosphorylation of a Ser791Ala Raptor mutant that cannot be phosphorylated by PKA (2). To test whether Akt, a well-known regulator of mTOR activity, contributes to the activation of mTOR signaling by Lira, we pre-treated GLP-1R stably expressing CHO cells with either of the Akt inhibitors Akt-i 1/2 and MK-2206 followed by treatment with Lira or forskolin (Fsk), a cAMP inducer and PKA activator. Pre-treatment with either Akt-i 1/2 or MK-2206 blocked mTOR activation by both Lira and Fsk. This suggests that the contribution of Akt to Lira-induced mTOR activation is likely downstream of cAMP production. Taken together, our results suggest a novel two-pronged, PKA-dependent mechanism for the stimulation of mTOR signaling following GLP-1R activation – directly via phosphorylation of Raptor and indirectly via stimulation of Akt. Future studies will assess the respective contributions and temporal dynamics of each of these pathways. Reference: (1) Burmeister et al., Am J Physiol Endocrinol Metab. 2017 Aug;313: E651–E662. (2) Liu et al., J Clin Invest. 2016;126(5):1704-1716.

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