Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake
Abstract Background Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy balance. In the brain, Glucagon-like peptide 1 (GLP-1), encoded by the proglucagon ‘Gcg’ gene, produced in a distinct population of neurons in the nucleus tractus solitarius (NTS), has b...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-022-00914-3 |
| _version_ | 1828100276022673408 |
|---|---|
| author | Ishnoor Singh Le Wang Baijuan Xia Ji Liu Azeddine Tahiri Abdelfattah El Ouaamari Michael B. Wheeler Zhiping P. Pang |
| author_facet | Ishnoor Singh Le Wang Baijuan Xia Ji Liu Azeddine Tahiri Abdelfattah El Ouaamari Michael B. Wheeler Zhiping P. Pang |
| author_sort | Ishnoor Singh |
| collection | DOAJ |
| description | Abstract Background Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy balance. In the brain, Glucagon-like peptide 1 (GLP-1), encoded by the proglucagon ‘Gcg’ gene, produced in a distinct population of neurons in the nucleus tractus solitarius (NTS), has been shown to regulate feeding behavior leading to the suppression of appetite. However, neuronal networks that mediate endogenous GLP-1 action in the CNS on feeding and energy balance are not well understood. Results We analyzed the distribution of GLP-1R-expressing neurons and axonal projections of NTS GLP-1-producing neurons in the mouse brain. GLP-1R neurons were found to be broadly distributed in the brain and specific forebrain regions, particularly the hypothalamus, including the arcuate nucleus of the hypothalamus (ARC), a brain region known to regulate energy homeostasis and feeding behavior, that receives dense NTSGcg neuronal projections. The impact of GLP-1 signaling in the ARC GLP-1R-expressing neurons and the impact of activation of ARC GLP-1R on food intake was examined. Application of GLP-1R specific agonist Exendin-4 (Exn-4) enhanced a proportion of the ARC GLP-1R-expressing neurons and pro-opiomelanocortin (POMC) neuronal action potential firing rates. Chemogenetic activation of the ARC GLP-1R neurons by using Cre-dependent hM3Dq AAV in the GLP-1R-ires-Cre mice, established that acute activation of the ARC GLP-1R neurons significantly suppressed food intake but did not have a strong impact on glucose homeostasis. Conclusions These results highlight the importance of central GLP-1 signaling in the ARC that express GLP-1R that upon activation, regulate feeding behavior. |
| first_indexed | 2024-04-11T08:26:56Z |
| format | Article |
| id | doaj.art-975c44ef885847bab42c855162866206 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-11T08:26:56Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-975c44ef885847bab42c8551628662062022-12-22T04:34:43ZengBMCCell & Bioscience2045-37012022-10-0112111410.1186/s13578-022-00914-3Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intakeIshnoor Singh0Le Wang1Baijuan Xia2Ji Liu3Azeddine Tahiri4Abdelfattah El Ouaamari5Michael B. Wheeler6Zhiping P. Pang7The Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyThe Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyThe Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyThe Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyThe Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyThe Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyDepartment of Physiology, University of TorontoThe Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New JerseyAbstract Background Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy balance. In the brain, Glucagon-like peptide 1 (GLP-1), encoded by the proglucagon ‘Gcg’ gene, produced in a distinct population of neurons in the nucleus tractus solitarius (NTS), has been shown to regulate feeding behavior leading to the suppression of appetite. However, neuronal networks that mediate endogenous GLP-1 action in the CNS on feeding and energy balance are not well understood. Results We analyzed the distribution of GLP-1R-expressing neurons and axonal projections of NTS GLP-1-producing neurons in the mouse brain. GLP-1R neurons were found to be broadly distributed in the brain and specific forebrain regions, particularly the hypothalamus, including the arcuate nucleus of the hypothalamus (ARC), a brain region known to regulate energy homeostasis and feeding behavior, that receives dense NTSGcg neuronal projections. The impact of GLP-1 signaling in the ARC GLP-1R-expressing neurons and the impact of activation of ARC GLP-1R on food intake was examined. Application of GLP-1R specific agonist Exendin-4 (Exn-4) enhanced a proportion of the ARC GLP-1R-expressing neurons and pro-opiomelanocortin (POMC) neuronal action potential firing rates. Chemogenetic activation of the ARC GLP-1R neurons by using Cre-dependent hM3Dq AAV in the GLP-1R-ires-Cre mice, established that acute activation of the ARC GLP-1R neurons significantly suppressed food intake but did not have a strong impact on glucose homeostasis. Conclusions These results highlight the importance of central GLP-1 signaling in the ARC that express GLP-1R that upon activation, regulate feeding behavior.https://doi.org/10.1186/s13578-022-00914-3Glucagon-like peptide-1HypothalamusPro-opiomelanocortinExendin-4ChemogeneticsGlucose tolerance |
| spellingShingle | Ishnoor Singh Le Wang Baijuan Xia Ji Liu Azeddine Tahiri Abdelfattah El Ouaamari Michael B. Wheeler Zhiping P. Pang Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake Cell & Bioscience Glucagon-like peptide-1 Hypothalamus Pro-opiomelanocortin Exendin-4 Chemogenetics Glucose tolerance |
| title | Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake |
| title_full | Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake |
| title_fullStr | Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake |
| title_full_unstemmed | Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake |
| title_short | Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake |
| title_sort | activation of arcuate nucleus glucagon like peptide 1 receptor expressing neurons suppresses food intake |
| topic | Glucagon-like peptide-1 Hypothalamus Pro-opiomelanocortin Exendin-4 Chemogenetics Glucose tolerance |
| url | https://doi.org/10.1186/s13578-022-00914-3 |
| work_keys_str_mv | AT ishnoorsingh activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT lewang activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT baijuanxia activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT jiliu activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT azeddinetahiri activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT abdelfattahelouaamari activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT michaelbwheeler activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake AT zhipingppang activationofarcuatenucleusglucagonlikepeptide1receptorexpressingneuronssuppressesfoodintake |