{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:09:45Z","timestamp":1760058585092,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2023R1A2C1003978","NRF-2021R1C1C2005067"],"award-info":[{"award-number":["NRF-2023R1A2C1003978","NRF-2021R1C1C2005067"]}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["NRF-2023R1A2C1003978","NRF-2021R1C1C2005067"],"award-info":[{"award-number":["NRF-2023R1A2C1003978","NRF-2021R1C1C2005067"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The adrenergic system plays an active role in modulating synaptic transmission in hypothalamic neurocircuitry. While \u03b12-adrenergic receptors are widely distributed in various organs and are involved in various physiological functions, their specific role in the regulation of energy metabolism in the brain remains incompletely understood. Herein, we investigated the functions of \u03b12-adrenergic receptors in the hypothalamus on energy metabolism in mice. Our study confirmed the expression of \u03b12-adrenergic receptors in hypothalamic dopaminergic neurons and assessed metabolic phenotypes, including food intake and energy expenditure, after treatment with guanabenz, an \u03b12-adrenergic receptor agonist. Guanabenz treatment significantly increased food intake (0.25 \u00b1 0.03 g vs. 0.98 \u00b1 0.05 g, p &lt; 0.001) and body weight (\u22120.1 \u00b1 0.04 g vs. 0.33 \u00b1 0.03 g, p &lt; 0.001) within 6 h post-treatment. Furthermore, guanabenz markedly elevated energy expenditure parameters, including respiratory exchange ratio (RER, 1.017 \u00b1 0.007 vs. 1.113 \u00b1 0.03, p &lt; 0.01) and carbon dioxide production (1.512 \u00b1 0.018 mL\/min vs. 1.635 \u00b1 0.036 mL\/min, p &lt; 0.05), compared to vehicle-treated controls. Furthermore, using chemogenetic techniques, we demonstrated that the altered metabolic phenotypes induced by guanabenz treatment were effectively reversed by inhibiting the activity of dopaminergic neurons in the hypothalamic arcuate nucleus (ARC) using a chemogenetic technique. Our findings suggest functional connectivity between hypothalamic \u03b12-adrenergic receptor signals and dopaminergic neurons in metabolic controls.<\/jats:p>","DOI":"10.3390\/ijms26083590","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T11:26:41Z","timestamp":1744284401000},"page":"3590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b12-Adrenergic Receptors in Hypothalamic Dopaminergic Neurons: Impact on Food Intake and Energy Expenditure"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-9645","authenticated-orcid":false,"given":"Byong Seo","family":"Park","sequence":"first","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea"},{"name":"Research Center of Brain-Machine Interface, Incheon National University, Incheon 22012, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Rim","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hara","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Kon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunggu","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center of Brain-Machine Interface, Incheon National University, Incheon 22012, Republic of Korea"},{"name":"Department of Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea"},{"name":"Research Center of Brain-Machine Interface, Incheon National University, Incheon 22012, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1096\/fj.08-105775","article-title":"Abundance and Stability of Complexes Containing Inactive G Protein-coupled Receptors and G Proteins","volume":"22","author":"Qin","year":"2008","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.2174\/157015909790031193","article-title":"Neuroplasticity Regulation by Noradrenaline in Mammalian Brain","volume":"7","author":"Marzo","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0163-7258(99)00032-7","article-title":"Localization and Trafficking of A2-Adrenergic Receptor Subtypes in Cells and Tissues","volume":"84","author":"Saunders","year":"1999","journal-title":"Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1046\/j.1365-2044.1999.00659.x","article-title":"Alpha-2 and Imidazoline Receptor agonistsTheir Pharmacology and Therapeutic Role","volume":"54","author":"Khan","year":"1999","journal-title":"Anaesthesia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.med.60.042307.110802","article-title":"The Expanded Biology of Serotonin","volume":"60","author":"Berger","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.33549\/physiolres.931903","article-title":"Serotonin Receptors\u2014From Molecular Biology to Clinical Applications","volume":"60","author":"Pytliak","year":"2011","journal-title":"Physiol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.cell.2019.05.048","article-title":"Regulation of Energy Expenditure by Brainstem GABA Neurons","volume":"178","author":"Schneeberger","year":"2019","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Flores, R.A., Dos-Santos, R.C., Steinbach, R., Rodrigues-Santos, I., de Jesus, A.A., Antunes-Rodrigues, J., and Paschoalini, M.A. (2021). \u03b1-1 Adrenoceptor Activation in the Dorsal Raphe Nucleus Decreases Food Intake in Fasted Rats. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.775070"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108397","DOI":"10.1016\/j.neuropharm.2020.108397","article-title":"Injections of the \u03b1-2 Adrenoceptor Agonist Clonidine into the Dorsal Raphe Nucleus Increases Food Intake in Satiated Rats","volume":"182","author":"Flores","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.tins.2007.06.004","article-title":"Is Dopamine a Physiologically Relevant Mediator of Feeding Behavior?","volume":"30","author":"Palmiter","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.yfrne.2009.10.004","article-title":"Metabolic Hormones, Dopamine Circuits, and Feeding","volume":"31","author":"Narayanan","year":"2010","journal-title":"Front. Neuroendocr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Coccurello, R., and Maccarrone, M. (2018). Hedonic Eating and the \u201cDelicious Circle\u201d: From Lipid-Derived Mediators to Brain Dopamine and Back. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00271"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Speranza, L., di Porzio, U., Viggiano, D., de Donato, A., and Volpicelli, F. (2021). Dopamine: The Neuromodulator of Long-Term Synaptic Plasticity, Reward and Movement Control. Cells, 10.","DOI":"10.3390\/cells10040735"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/nn.4372","article-title":"Hypothalamic Arcuate Nucleus Tyrosine Hydroxylase Neurons Play Orexigenic Role in Energy Homeostasis","volume":"19","author":"Zhang","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Na, J., Park, B.S., Jang, D., Kim, D., Tu, T.H., Ryu, Y., Ha, C.M., Koch, M., Yang, S., and Kim, J.G. (2022). Distinct Firing Activities of the Hypothalamic Arcuate Nucleus Neurons to Appetite Hormones. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052609"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8905","DOI":"10.1074\/jbc.M109.079590","article-title":"Enhanced Hypothalamic Leptin Signaling in Mice Lacking Dopamine D2 Receptors","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111718","DOI":"10.1016\/j.celrep.2022.111718","article-title":"Food-Induced Dopamine Signaling in AgRP Neurons Promotes Feeding","volume":"41","author":"Zhang","year":"2022","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1210\/jc.2004-1356","article-title":"\u03922-Adrenergic Receptor Polymorphisms and Salbutamol-Stimulated Energy Expenditure","volume":"90","author":"Oomen","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E775","DOI":"10.1152\/ajpendo.00175.2003","article-title":"Effect of \u03921- and \u03922-Adrenergic Stimulation on Energy Expenditure, Substrate Oxidation, and UCP3 Expression in Humans","volume":"285","author":"Hoeks","year":"2003","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.2337\/dbi24-0002","article-title":"NMDA Receptors in POMC Neurons Connect Exercise with Insulin Sensitivity","volume":"73","author":"Portillo","year":"2024","journal-title":"Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8678","DOI":"10.1523\/JNEUROSCI.0798-17.2017","article-title":"AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons","volume":"37","author":"Essner","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1038\/s41467-021-23846-x","article-title":"Deciphering an AgRP-Serotoninergic Neural Circuit in Distinct Control of Energy Metabolism from Feeding","volume":"12","author":"Han","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s11011-019-00442-z","article-title":"Re-Examining the Role of Ventral Tegmental Area Dopaminergic Neurons in Motor Activity and Reinforcement by Chemogenetic and Optogenetic Manipulation in Mice","volume":"34","author":"Jing","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"773","DOI":"10.32598\/bcn.11.6.2226.1","article-title":"Ventral Tegmental Area Microinjected-SKF38393 Increases Regular Chow Intake in 18 Hours Food-Deprived Rats","volume":"11","author":"Rad","year":"2020","journal-title":"Basic Clin. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e25770","DOI":"10.7554\/eLife.25770","article-title":"Antagonistic Modulation of NPY\/AgRP and POMC Neurons in the Arcuate Nucleus by Noradrenalin","volume":"6","author":"Paeger","year":"2017","journal-title":"eLife"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41467-023-44633-w","article-title":"Lateral Hypothalamic Glutamatergic Inputs to VTA Glutamatergic Neurons Mediate Prioritization of Innate Defensive Behavior over Feeding","volume":"15","author":"Barbano","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3803\/EnM.2021.979","article-title":"Dopaminergic Control of the Feeding Circuit","volume":"36","author":"Baik","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"114236","DOI":"10.1016\/j.physbeh.2023.114236","article-title":"Metabolic Hormone Action in the VTA: Reward-Directed Behavior and Mechanistic Insights","volume":"268","author":"Geisler","year":"2023","journal-title":"Physiol. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1084\/jem.20180653","article-title":"Microglial Translational Profiling Reveals a Convergent APOE Pathway from Aging, Amyloid, and Tau","volume":"215","author":"Kang","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13939","DOI":"10.1073\/pnas.0907143106","article-title":"Cell-Type-Specific Isolation of Ribosome-Associated mRNA from Complex Tissues","volume":"106","author":"Sanz","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12974-020-01846-w","article-title":"Function of Astrocyte MyD88 in High-Fat-Diet-Induced Hypothalamic Inflammation","volume":"17","author":"Jin","year":"2020","journal-title":"J. Neuroinflamm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:29Z","timestamp":1760029949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083590"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083590","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,4,10]]}}}