{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:55:18Z","timestamp":1793256918952,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor \u03b1-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL\/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius. Thus, BDNF<jats:sup>mNTS<\/jats:sup> neurons are required for the weight-reducing actions of both GDF15 and the GLP1RA, Exendin-4. Moreover, acute activation of BDNF<jats:sup>mNTS<\/jats:sup> neurons is sufficient to reduce food intake and drive fatty acid oxidation and might provide a route for longer-term weight loss.<\/jats:p>","DOI":"10.1038\/s41467-024-54367-y","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T15:52:50Z","timestamp":1735573970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Brainstem BDNF neurons are downstream of GFRAL\/GLP1R signalling"],"prefix":"10.1038","volume":"15","author":[{"given":"Claire H.","family":"Feetham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Collabolletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2573-7140","authenticated-orcid":false,"given":"Amy A.","family":"Worth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Shoop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Groom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Court","family":"Harding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Boutagouga Boudjadja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Coskun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Emmerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3502-4251","authenticated-orcid":false,"given":"Giuseppe","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-5473","authenticated-orcid":false,"given":"Simon M.","family":"Luckman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"54367_CR1","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/s41574-021-00529-7","volume":"17","author":"D Wang","year":"2021","unstructured":"Wang, D. et al. GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease. Nat. Rev. Endocrinol. 17, 592\u2013607 (2021).","journal-title":"Nat. Rev. Endocrinol."},{"key":"54367_CR2","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1146\/annurev-physiol-022020-045449","volume":"83","author":"SN Breit","year":"2021","unstructured":"Breit, S. N., Brown, D. A. & Tsai, V. W. The GDF15-GFRAL pathway in health and metabolic disease: friend or foe? Annu. Rev. Physiol. 83, 127\u2013151 (2021).","journal-title":"Annu. Rev. Physiol."},{"key":"54367_CR3","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/nm.4392","volume":"23","author":"SE Mullican","year":"2017","unstructured":"Mullican, S. E. et al. GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat. Med. 23, 1150\u20131157 (2017).","journal-title":"Nat. Med."},{"key":"54367_CR4","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1038\/nm.4394","volume":"23","author":"L Yang","year":"2017","unstructured":"Yang, L. et al. GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat. Med. 23, 1158\u20131166 (2017).","journal-title":"Nat. Med."},{"key":"54367_CR5","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/nm.4393","volume":"23","author":"PJ Emmerson","year":"2017","unstructured":"Emmerson, P. J. et al. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat. Med. 23, 1215\u20131219 (2017).","journal-title":"Nat. Med."},{"key":"54367_CR6","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature24042","volume":"550","author":"JY Hsu","year":"2017","unstructured":"Hsu, J. Y. et al. Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15. Nature 550, 255\u2013259 (2017).","journal-title":"Nature"},{"key":"54367_CR7","doi-asserted-by":"publisher","first-page":"e0201584","DOI":"10.1371\/journal.pone.0201584","volume":"13","author":"T Tran","year":"2018","unstructured":"Tran, T., Yang, J., Gardner, J. & Xiong, Y. GDF15 deficiency promotes high fat diet-induced obesity in mice. PLoS ONE 13, e0201584 (2018).","journal-title":"PLoS ONE"},{"key":"54367_CR8","doi-asserted-by":"publisher","first-page":"e55174","DOI":"10.1371\/journal.pone.0055174","volume":"8","author":"VW Tsai","year":"2013","unstructured":"Tsai, V. W. et al. TGF-b superfamily cytokine MIC-1\/GDF15 is a physiological appetite and body weight regulator. PLoS ONE 8, e55174 (2013).","journal-title":"PLoS ONE"},{"key":"54367_CR9","doi-asserted-by":"publisher","first-page":"e0168416","DOI":"10.1371\/journal.pone.0168416","volume":"12","author":"JK Low","year":"2017","unstructured":"Low, J. K. et al. First behavioural characterisation of a knockout mouse model for the transforming growth factor (TGF)-beta superfamily cytokine, MIC-1\/GDF15. PLoS ONE 12, e0168416 (2017).","journal-title":"PLoS ONE"},{"key":"54367_CR10","doi-asserted-by":"publisher","unstructured":"Worth, A. A. et al. The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling. eLife 9 https:\/\/doi.org\/10.7554\/eLife.55164 (2020).","DOI":"10.7554\/eLife.55164"},{"key":"54367_CR11","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cmet.2018.12.016","volume":"29","author":"S Patel","year":"2019","unstructured":"Patel, S. et al. GDF15 provides an endocrine signal of nutritional stress in mice and humans. Cell Metab. 29, 707\u2013718.e708 (2019).","journal-title":"Cell Metab."},{"key":"54367_CR12","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/j.cell.2019.07.033","volume":"178","author":"HH Luan","year":"2019","unstructured":"Luan, H. H. et al. GDF15 is an inflammation-induced central mediator of tissue tolerance. Cell 178, 1231\u20131244.e1211 (2019).","journal-title":"Cell"},{"key":"54367_CR13","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1038\/s41591-020-0945-x","volume":"26","author":"R Suriben","year":"2020","unstructured":"Suriben, R. et al. Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice. Nat. Med. 26, 1264\u20131270 (2020).","journal-title":"Nat. Med."},{"key":"54367_CR14","doi-asserted-by":"publisher","unstructured":"Lockhart, S. M., Saudek, V. & O\u2019Rahilly, S. GDF15: a hormone conveying somatic distress to the brain. Endocr. Rev. 41 https:\/\/doi.org\/10.1210\/endrev\/bnaa007 (2020).","DOI":"10.1210\/endrev\/bnaa007"},{"key":"54367_CR15","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.cmet.2019.12.004","volume":"31","author":"T Borner","year":"2020","unstructured":"Borner, T. et al. GDF15 induces anorexia through nausea and emesis. Cell Metab. 31, 351\u2013362.e355 (2020).","journal-title":"Cell Metab."},{"key":"54367_CR16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41586-023-06249-4","volume":"619","author":"D Wang","year":"2023","unstructured":"Wang, D. et al. GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature 619, 143\u2013150 (2023).","journal-title":"Nature"},{"key":"54367_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.molmet.2019.01.003","volume":"21","author":"H Frikke-Schmidt","year":"2019","unstructured":"Frikke-Schmidt, H. et al. GDF15 acts synergistically with liraglutide but is not necessary for the weight loss induced by bariatric surgery in mice. Mol. Metab. 21, 13\u201321 (2019).","journal-title":"Mol. Metab."},{"key":"54367_CR18","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.neuron.2020.11.010","volume":"109","author":"C Zhang","year":"2021","unstructured":"Zhang, C. et al. Area postrema cell types that mediate nausea-associated behaviors. Neuron 109, 461\u2013472.e465 (2021).","journal-title":"Neuron"},{"key":"54367_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101407","volume":"55","author":"A Costa","year":"2022","unstructured":"Costa, A. et al. Anorectic and aversive effects of GLP\u22121 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation. Mol. Metab. 55, 101407 (2022).","journal-title":"Mol. Metab."},{"key":"54367_CR20","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1111\/dom.14663","volume":"24","author":"M Ghidewon","year":"2022","unstructured":"Ghidewon, M. et al. Growth differentiation factor 15 (GDF15) and semaglutide inhibit food intake and body weight through largely distinct, additive mechanisms. Diab. Obes. Metab. 24, 1010\u20131020 (2022).","journal-title":"Diab. Obes. Metab."},{"key":"54367_CR21","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nature12596","volume":"503","author":"ME Carter","year":"2013","unstructured":"Carter, M. E., Soden, M. E., Zweifel, L. S. & Palmiter, R. D. Genetic identification of a neural circuit that suppresses appetite. Nature 503, 111\u2013114 (2013).","journal-title":"Nature"},{"key":"54367_CR22","doi-asserted-by":"publisher","first-page":"11094","DOI":"10.1523\/JNEUROSCI.0440-15.2015","volume":"35","author":"AL Alhadeff","year":"2015","unstructured":"Alhadeff, A. L., Holland, R. A., Nelson, A., Grill, H. J. & De Jonghe, B. C. Glutamate receptors in the central nucleus of the amygdala mediate cisplatin-induced malaise and energy balance dysregulation through direct hindbrain projections. J. Neurosci. 35, 11094\u201311104 (2015).","journal-title":"J. Neurosci."},{"key":"54367_CR23","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1038\/nn.3767","volume":"17","author":"H Cai","year":"2014","unstructured":"Cai, H., Haubensak, W., Anthony, T. E. & Anderson, D. J. Central amygdala PKC-delta(+) neurons mediate the influence of multiple anorexigenic signals. Nat. Neurosci. 17, 1240\u20131248 (2014).","journal-title":"Nat. Neurosci."},{"key":"54367_CR24","doi-asserted-by":"publisher","unstructured":"Sabatini, P. V. et al. GFRAL-expressing neurons suppress food intake via aversive pathways. Proc. Natl Acad. Sci. USA 118 https:\/\/doi.org\/10.1073\/pnas.2021357118 (2021).","DOI":"10.1073\/pnas.2021357118"},{"key":"54367_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110953","volume":"39","author":"C Zhang","year":"2022","unstructured":"Zhang, C., Vincelette, L. K., Reimann, F. & Liberles, S. D. A brainstem circuit for nausea suppression. Cell Rep. 39, 110953 (2022).","journal-title":"Cell Rep."},{"key":"54367_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101240","volume":"53","author":"GKC Dowsett","year":"2021","unstructured":"Dowsett, G. K. C. et al. A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing. Mol. Metab. 53, 101240 (2021).","journal-title":"Mol. Metab."},{"key":"54367_CR27","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s42255-021-00363-1","volume":"3","author":"MQ Ludwig","year":"2021","unstructured":"Ludwig, M. Q. et al. A genetic map of the mouse dorsal vagal complex and its role in obesity. Nat. Metab. 3, 530\u2013545 (2021).","journal-title":"Nat. Metab."},{"key":"54367_CR28","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1172\/JCI72434","volume":"124","author":"S Sisley","year":"2014","unstructured":"Sisley, S. et al. Neuronal GLP1R mediates liraglutide\u2019s anorectic but not glucose-lowering effect. J. Clin. Invest. 124, 2456\u20132463 (2014).","journal-title":"J. Clin. Invest."},{"key":"54367_CR29","doi-asserted-by":"publisher","unstructured":"Cimino, I. et al. Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15. Proc. Natl Acad. Sci. USA 118 https:\/\/doi.org\/10.1073\/pnas.2106868118 (2021).","DOI":"10.1073\/pnas.2106868118"},{"key":"54367_CR30","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0006-8993(03)03117-2","volume":"985","author":"S Sarkar","year":"2003","unstructured":"Sarkar, S., Fekete, C., Legradi, G. & Lechan, R. M. Glucagon like peptide-1 (7-36) amide (GLP-1) nerve terminals densely innervate corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. Brain Res. 985, 163\u2013168 (2003).","journal-title":"Brain Res."},{"key":"54367_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113960","volume":"43","author":"L Engstrom Ruud","year":"2024","unstructured":"Engstrom Ruud, L. et al. Activation of GFRAL(+) neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor. Cell Rep. 43, 113960 (2024).","journal-title":"Cell Rep."},{"key":"54367_CR32","doi-asserted-by":"publisher","unstructured":"Xiong, Y. et al. Long-acting MIC-1\/GDF15 molecules to treat obesity: evidence from mice to monkeys. Sci. Transl. Med. 9 https:\/\/doi.org\/10.1126\/scitranslmed.aan8732 (2017).","DOI":"10.1126\/scitranslmed.aan8732"},{"key":"54367_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107543","volume":"31","author":"T Borner","year":"2020","unstructured":"Borner, T. et al. GDF15 induces an aversive visceral malaise state that drives anorexia and weight loss. Cell Rep. 31, 107543 (2020).","journal-title":"Cell Rep."},{"key":"54367_CR34","doi-asserted-by":"publisher","first-page":"4699","DOI":"10.1016\/j.cub.2022.09.017","volume":"32","author":"M Boutagouga Boudjadja","year":"2022","unstructured":"Boutagouga Boudjadja, M. et al. Hypothalamic AgRP neurons exert top-down control on systemic TNF-alpha release during endotoxemia. Curr. Biol. 32, 4699\u20134706.e4694 (2022).","journal-title":"Curr. Biol."},{"key":"54367_CR35","doi-asserted-by":"publisher","unstructured":"D\u2019Agostino, G. et al. Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. eLife 5 https:\/\/doi.org\/10.7554\/eLife.12225 (2016).","DOI":"10.7554\/eLife.12225"},{"key":"54367_CR36","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.neuroscience.2017.06.049","volume":"358","author":"CW Roman","year":"2017","unstructured":"Roman, C. W., Sloat, S. R. & Palmiter, R. D. A tale of two circuits: CCK(NTS) neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions. Neuroscience 358, 316\u2013324 (2017).","journal-title":"Neuroscience"},{"key":"54367_CR37","doi-asserted-by":"publisher","first-page":"4600","DOI":"10.1210\/en.2012-1282","volume":"153","author":"AS Garfield","year":"2012","unstructured":"Garfield, A. S. et al. Neurochemical characterization of body weight-regulating leptin receptor neurons in the nucleus of the solitary tract. Endocrinology 153, 4600\u20134607 (2012).","journal-title":"Endocrinology"},{"key":"54367_CR38","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.cmet.2023.06.009","volume":"35","author":"SN Breit","year":"2023","unstructured":"Breit, S. N. et al. GDF15 enhances body weight and adiposity reduction in obese mice by leveraging the leptin pathway. Cell Metab. 35, 1341\u20131355.e1343 (2023).","journal-title":"Cell Metab."},{"key":"54367_CR39","doi-asserted-by":"publisher","first-page":"5612","DOI":"10.1210\/en.2005-0419","volume":"146","author":"B Bariohay","year":"2005","unstructured":"Bariohay, B., Lebrun, B., Moyse, E. & Jean, A. Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex. Endocrinology 146, 5612\u20135620 (2005).","journal-title":"Endocrinology"},{"key":"54367_CR40","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1210\/en.2008-1184","volume":"150","author":"B Bariohay","year":"2009","unstructured":"Bariohay, B. et al. Brain-derived neurotrophic factor\/tropomyosin-related kinase receptor type B signaling is a downstream effector of the brainstem melanocortin system in food intake control. Endocrinology 150, 2646\u20132653 (2009).","journal-title":"Endocrinology"},{"key":"54367_CR41","doi-asserted-by":"publisher","first-page":"84028","DOI":"10.18632\/oncotarget.21062","volume":"8","author":"L Shen","year":"2017","unstructured":"Shen, L., Wang, D. Q. H., Xu, M., Woods, S. C. & Liu, M. BDNF\/TrkB signaling mediates the anorectic action of estradiol in the nucleus tractus solitarius. Oncotarget 8, 84028\u201384038 (2017).","journal-title":"Oncotarget"},{"key":"54367_CR42","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.2337\/diabetes.50.11.2530","volume":"50","author":"PJ Larsen","year":"2001","unstructured":"Larsen, P. J., Fledelius, C., Knudsen, L. B. & Tang-Christensen, M. Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes 50, 2530\u20132539 (2001).","journal-title":"Diabetes"},{"key":"54367_CR43","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/j.1463-1326.2012.01557.x","volume":"14","author":"J Jelsing","year":"2012","unstructured":"Jelsing, J. et al. Liraglutide: short-lived effect on gastric emptying - long lasting effects on body weight. Diab. Obes. Metab. 14, 531\u2013538 (2012).","journal-title":"Diab. Obes. Metab."},{"key":"54367_CR44","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","volume":"18","author":"T Coskun","year":"2018","unstructured":"Coskun, T. et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol. Metab. 18, 3\u201314 (2018).","journal-title":"Mol. Metab."},{"key":"54367_CR45","doi-asserted-by":"publisher","unstructured":"Gabery, S. et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight 5 https:\/\/doi.org\/10.1172\/jci.insight.133429 (2020).","DOI":"10.1172\/jci.insight.133429"},{"key":"54367_CR46","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.cmet.2022.12.011","volume":"35","author":"O Benichou","year":"2023","unstructured":"Benichou, O. et al. Discovery, development, and clinical proof of mechanism of LY3463251, a long-acting GDF15 receptor agonist. Cell Metab. 35, 274\u2013286.e210 (2023).","journal-title":"Cell Metab."},{"key":"54367_CR47","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1146\/annurev.physiol.66.032102.115105","volume":"66","author":"F Geiser","year":"2004","unstructured":"Geiser, F. Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu. Rev. Physiol. 66, 239\u2013274 (2004).","journal-title":"Annu. Rev. Physiol."},{"key":"54367_CR48","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.resp.2004.03.014","volume":"141","author":"G Heldmaier","year":"2004","unstructured":"Heldmaier, G., Ortmann, S. & Elvert, R. Natural hypometabolism during hibernation and daily torpor in mammals. Respir. Physiol. Neurobiol. 141, 317\u2013329 (2004).","journal-title":"Respir. Physiol. Neurobiol."},{"key":"54367_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51841-2","volume":"9","author":"T Hitrec","year":"2019","unstructured":"Hitrec, T. et al. Neural control of fasting-induced torpor in mice. Sci. Rep. 9, 15462 (2019).","journal-title":"Sci. Rep."},{"key":"54367_CR50","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41586-020-2163-6","volume":"583","author":"TM Takahashi","year":"2020","unstructured":"Takahashi, T. M. et al. A discrete neuronal circuit induces a hibernation-like state in rodents. Nature 583, 109\u2013114 (2020).","journal-title":"Nature"},{"key":"54367_CR51","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41586-020-2387-5","volume":"583","author":"S Hrvatin","year":"2020","unstructured":"Hrvatin, S. et al. Neurons that regulate mouse torpor. Nature 583, 115\u2013121 (2020).","journal-title":"Nature"},{"key":"54367_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20050-1","volume":"11","author":"Z Zhang","year":"2020","unstructured":"Zhang, Z. et al. Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice. Nat. Commun. 11, 6378 (2020).","journal-title":"Nat. Commun."},{"key":"54367_CR53","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.cell.2019.05.048","volume":"178","author":"M Schneeberger","year":"2019","unstructured":"Schneeberger, M. et al. Regulation of energy expenditure by brainstem GABA neurons. Cell 178, 672\u2013685.e612 (2019).","journal-title":"Cell"},{"key":"54367_CR54","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1016\/j.cmet.2023.07.010","volume":"35","author":"JE Campbell","year":"2023","unstructured":"Campbell, J. E. et al. GIPR\/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications. Cell Metab. 35, 1519\u20131529 (2023).","journal-title":"Cell Metab."},{"key":"54367_CR55","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.cmet.2014.07.022","volume":"20","author":"GT Dodd","year":"2014","unstructured":"Dodd, G. T. et al. The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus. Cell Metab. 20, 639\u2013649 (2014).","journal-title":"Cell Metab."},{"key":"54367_CR56","unstructured":"Paxinos, G. & Franklin, K. B. J. The Mouse Brain (Academic Press, 2001)."},{"key":"54367_CR57","first-page":"628","volume":"55","author":"KN Frayn","year":"1983","unstructured":"Frayn, K. N. Calculation of substrate oxidation rates in vivo from gaseous exchange. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 55, 628\u2013634 (1983).","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54367-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54367-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54367-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T04:58:28Z","timestamp":1735621108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54367-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["54367"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-54367-y","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]},"assertion":[{"value":"16 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: PJE and TC are paid employees of Eli Lilly. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10749"}}