Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons
Background Glucagon-like peptide-1 (GLP-1) is an incretin known for its anti-obesity effects, and several effective drugs targeting GLP-1 receptors (GLP-1Rs) have recently been developed to treat obesity. Although GLP-1Rs are expressed by various populations of central neurons, it is still unclear w...
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Korean Endocrine Society
2025-06-01
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| Series: | Endocrinology and Metabolism |
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| Online Access: | http://www.e-enm.org/upload/pdf/enm-2024-2185.pdf |
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| author | Sujin Yoo Eun-Seon Yoo Jae Il Kim Jong-Woo Sohn |
| author_facet | Sujin Yoo Eun-Seon Yoo Jae Il Kim Jong-Woo Sohn |
| author_sort | Sujin Yoo |
| collection | DOAJ |
| description | Background Glucagon-like peptide-1 (GLP-1) is an incretin known for its anti-obesity effects, and several effective drugs targeting GLP-1 receptors (GLP-1Rs) have recently been developed to treat obesity. Although GLP-1Rs are expressed by various populations of central neurons, it is still unclear which specific populations mediate the anti-obesity effects of GLP-1R agonists. Methods In this study, we utilized the previously reported GLP-1R agonist, exendin-4(1-32)K-capric acid (Ex-4c), and conducted whole-cell patch-clamp recordings, immunohistochemistry experiments, and in vivo food intake measurements. Results Our findings indicate that the appetite-suppressing effects of Ex-4c depend on pro-opiomelanocortin (POMC) neurons. Fos immunochemistry experiments and whole-cell patch-clamp recordings showed that Ex-4c activated POMC neurons in the arcuate nucleus of the hypothalamus. Additionally, we observed that Ex-4c stimulated GLP-1Rs and activated the protein kinase A (PKA)-dependent signaling pathway, which in turn closed putative adenosine triphosphate-sensitive K+ (KATP) channels, leading to the depolarization of POMC neurons. Conclusion Our results demonstrate that the appetite-suppressing effects of Ex-4c are mediated through the activation of arcuate POMC neurons. Furthermore, the PKA-dependent closure of putative KATP conductance is identified as the cellular mechanism responsible for the activation of POMC neurons. |
| format | Article |
| id | doaj-art-c38972ed43d14ea4857a0ce8f1d1c4b3 |
| institution | OA Journals |
| issn | 2093-596X 2093-5978 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj-art-c38972ed43d14ea4857a0ce8f1d1c4b32025-08-20T02:37:36ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782025-06-0140343444710.3803/EnM.2024.21852602Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin NeuronsSujin Yoo0Eun-Seon Yoo1Jae Il Kim2Jong-Woo Sohn3 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, KoreaBackground Glucagon-like peptide-1 (GLP-1) is an incretin known for its anti-obesity effects, and several effective drugs targeting GLP-1 receptors (GLP-1Rs) have recently been developed to treat obesity. Although GLP-1Rs are expressed by various populations of central neurons, it is still unclear which specific populations mediate the anti-obesity effects of GLP-1R agonists. Methods In this study, we utilized the previously reported GLP-1R agonist, exendin-4(1-32)K-capric acid (Ex-4c), and conducted whole-cell patch-clamp recordings, immunohistochemistry experiments, and in vivo food intake measurements. Results Our findings indicate that the appetite-suppressing effects of Ex-4c depend on pro-opiomelanocortin (POMC) neurons. Fos immunochemistry experiments and whole-cell patch-clamp recordings showed that Ex-4c activated POMC neurons in the arcuate nucleus of the hypothalamus. Additionally, we observed that Ex-4c stimulated GLP-1Rs and activated the protein kinase A (PKA)-dependent signaling pathway, which in turn closed putative adenosine triphosphate-sensitive K+ (KATP) channels, leading to the depolarization of POMC neurons. Conclusion Our results demonstrate that the appetite-suppressing effects of Ex-4c are mediated through the activation of arcuate POMC neurons. Furthermore, the PKA-dependent closure of putative KATP conductance is identified as the cellular mechanism responsible for the activation of POMC neurons.http://www.e-enm.org/upload/pdf/enm-2024-2185.pdfincretinshypothalamuselectrophysiologyimmunohistochemistryappetiteobesity |
| spellingShingle | Sujin Yoo Eun-Seon Yoo Jae Il Kim Jong-Woo Sohn Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons Endocrinology and Metabolism incretins hypothalamus electrophysiology immunohistochemistry appetite obesity |
| title | Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons |
| title_full | Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons |
| title_fullStr | Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons |
| title_full_unstemmed | Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons |
| title_short | Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons |
| title_sort | exendin 4 1 32 k capric acid a glucagon like peptide 1 receptor agonist suppresses food intake via arcuate pro opiomelanocortin neurons |
| topic | incretins hypothalamus electrophysiology immunohistochemistry appetite obesity |
| url | http://www.e-enm.org/upload/pdf/enm-2024-2185.pdf |
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