Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation
- PMID: 21356521
- PMCID: PMC3108145
- DOI: 10.1016/j.cmet.2011.02.001
Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation
Erratum in
-
Intracellular Signals Mediating the Food Intake-Suppressive Effects of Hindbrain Glucagon-like Peptide-1 Receptor Activation.Cell Metab. 2016 Apr 12;23(4):745. doi: 10.1016/j.cmet.2016.02.010. Cell Metab. 2016. PMID: 27076083 No abstract available.
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) activation within the nucleus tractus solitarius (NTS) suppresses food intake and body weight (BW), but the intracellular signals mediating these effects are unknown. Here, hindbrain (fourth i.c.v.) GLP-1R activation by Exendin-4 (Ex-4) increased PKA and MAPK activity and decreased phosphorylation of AMPK in NTS. PKA and MAPK signaling contribute to food intake and BW suppression by Ex-4, as inhibitors RpcAMP and U0126 (fourth i.c.v.), respectively, attenuated Ex-4's effects. Hindbrain GLP-1R activation inhibited feeding by reducing meal number, not meal size. This effect was attenuated with stimulation of AMPK activity by AICAR (fourth i.c.v.). The PKA, MAPK, and AMPK signaling responses by Ex-4 were present in immortalized GLP-1R-expressing neurons (GT1-7). In conclusion, hindbrain GLP-1R activation suppresses food intake and BW through coordinated PKA-mediated suppression of AMPK and activation of MAPK. Pharmacotherapies targeting these signaling pathways, which mediate intake-suppressive effects of CNS GLP-1R activation, may prove efficacious in treating obesity.
Copyright © 2011 Elsevier Inc. All rights reserved.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f5.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f6.gif)
![Figure 7](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3108145/bin/nihms280157f7.gif)
Similar articles
-
Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt.Am J Physiol Endocrinol Metab. 2013 Sep 15;305(6):E751-9. doi: 10.1152/ajpendo.00367.2013. Epub 2013 Jul 30. Am J Physiol Endocrinol Metab. 2013. PMID: 23900416 Free PMC article.
-
Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling.Endocrinology. 2009 Jun;150(6):2654-9. doi: 10.1210/en.2008-1479. Epub 2009 Mar 5. Endocrinology. 2009. PMID: 19264875 Free PMC article.
-
Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose.Am J Physiol Endocrinol Metab. 2013 Apr 1;304(7):E677-85. doi: 10.1152/ajpendo.00446.2012. Epub 2013 Jan 22. Am J Physiol Endocrinol Metab. 2013. PMID: 23341495
-
Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding.Am J Physiol Regul Integr Comp Physiol. 2014 Aug 15;307(4):R465-70. doi: 10.1152/ajpregu.00179.2014. Epub 2014 Jun 18. Am J Physiol Regul Integr Comp Physiol. 2014. PMID: 24944243 Free PMC article.
-
The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake.Int J Obes (Lond). 2009 Apr;33 Suppl 1:S11-5. doi: 10.1038/ijo.2009.10. Int J Obes (Lond). 2009. PMID: 19363500 Review.
Cited by
-
Recent Research on Mechanisms of Feeding Regulation in Chicks.J Poult Sci. 2024 Apr 26;61:2024012. doi: 10.2141/jpsa.2024012. eCollection 2024. J Poult Sci. 2024. PMID: 38681189 Free PMC article. Review.
-
Targeting GLP-1 receptors to reduce nicotine use disorder: Preclinical and clinical evidence.Physiol Behav. 2024 Jul 1;281:114565. doi: 10.1016/j.physbeh.2024.114565. Epub 2024 Apr 23. Physiol Behav. 2024. PMID: 38663460 Free PMC article. Review.
-
Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide.Elife. 2023 Nov 6;12:e80944. doi: 10.7554/eLife.80944. Elife. 2023. PMID: 37930356 Free PMC article.
-
The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1.Sci Adv. 2023 Sep 22;9(38):eadh0980. doi: 10.1126/sciadv.adh0980. Epub 2023 Sep 20. Sci Adv. 2023. PMID: 37729419 Free PMC article.
-
Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro.Sci Rep. 2023 May 16;13(1):7948. doi: 10.1038/s41598-023-34070-6. Sci Rep. 2023. PMID: 37193712 Free PMC article.
References
-
- Chelikani PK, Haver AC, Reidelberger RD. Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol. 2005;288:R1695–1706. - PubMed
-
- Daniels D, Patten CS, Roth JD, Yee DK, Fluharty SJ. Melanocortin receptor signaling through mitogen-activated protein kinase in vitro and in rat hypothalamus. Brain Res. 2003;986:1–11. - PubMed
-
- Daniels D, Yee DK, Faulconbridge LF, Fluharty SJ. Divergent behavioral roles of angiotensin receptor intracellular signaling cascades. Endocrinology. 2005;146:5552–5560. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- DK21397/DK/NIDDK NIH HHS/United States
- R56 DK021397/DK/NIDDK NIH HHS/United States
- DK082417/DK/NIDDK NIH HHS/United States
- R01 DK021397/DK/NIDDK NIH HHS/United States
- 5P30DK019525/DK/NIDDK NIH HHS/United States
- K01 DK085435-01/DK/NIDDK NIH HHS/United States
- F32 DK077484/DK/NIDDK NIH HHS/United States
- R01 DK082417/DK/NIDDK NIH HHS/United States
- DK085435/DK/NIDDK NIH HHS/United States
- K01 DK085435/DK/NIDDK NIH HHS/United States
- DK077484/DK/NIDDK NIH HHS/United States
- P30 DK019525/DK/NIDDK NIH HHS/United States
LinkOut - more resources
Full Text Sources