{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:17:53Z","timestamp":1792135073357,"version":"4.4.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"a Grant-in-Aid for Young Scientists (B) from JSPS KAKENHI","award":["No.20790665"],"award-info":[{"award-number":["No.20790665"]}]},{"name":"a Grant-in-Aid for Scientific Research (C) from JSPS KAKENHI","award":["No.20K08898"],"award-info":[{"award-number":["No.20K08898"]}]},{"name":"the Kato Memorial Bioscience Foundation"},{"name":"the Foundation for Growth Science"},{"name":"the Ishibashi Foundation for the Promotion of Science"},{"name":"the Takeda Scientific Foundation"},{"name":"the Kobayashi Foundation","award":["No.215"],"award-info":[{"award-number":["No.215"]}]},{"name":"the Program for the Promotion of Basic and Applied Research for Innovations in Bio-oriented Industry"},{"name":"a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ghrelin, a circulating orexigenic hormone secreted from the stomach, stimulates appetite and food intake by activating the hypothalamic arcuate nucleus. Administration of exogenous ghrelin exerts anabolic effects, causing weight gain, increased adiposity, and decreased metabolism. Body temperature (BT), which is determined by the balance of heat production and heat loss, must be strictly regulated to maintain proper cellular function and metabolism. However, the role of ghrelin in thermoregulation remains unclear. In this study, we found that ghrelin was essential for decreasing BT when mice are placed under calorie restriction. Elevated ghrelin concentrations induced by fasting correlated with significant decreases in BT, a hibernation-like state called torpor. Ghrelin-deficient (<jats:italic>Ghrl<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) animals could not enter torpor. The BT of <jats:italic>Ghrl<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice also remained high under restricted feeding, but the animals gradually entered precipitous hypothermia, indicating thermoregulatory impairment. These effects of ghrelin on thermoregulation were the result of suppression of sympathetic nervous system activity input to brown adipose tissue; in the absence of ghrelin, it was not possible to suppress uncoupling protein 1 (<jats:italic>ucp1<\/jats:italic>) expression and decrease BT in low-energy states. Together, these findings demonstrate that ghrelin is an essential circulating hormone involved in lowering BT.<\/jats:p>","DOI":"10.1038\/s41598-021-97440-y","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T10:04:04Z","timestamp":1631527444000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Thermoregulatory role of ghrelin in the induction of torpor under a restricted feeding condition"],"prefix":"10.1038","volume":"11","author":[{"given":"Takahiro","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanae","family":"Oishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Koga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kangawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayasu","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"97440_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/45230","author":"M Kojima","year":"1999","unstructured":"Kojima, M. et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature https:\/\/doi.org\/10.1038\/45230 (1999).","journal-title":"Nature"},{"key":"97440_CR2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1040","author":"H Ariyasu","year":"2010","unstructured":"Ariyasu, H. et al. A postweaning reduction in circulating ghrelin temporarily alters growth hormone (GH) responsiveness to GH-releasing hormone in male mice but does not affect somatic growth. Endocrinology. https:\/\/doi.org\/10.1210\/en.2009-1040 (2010).","journal-title":"Endocrinology"},{"key":"97440_CR3","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.22158","author":"A Asakawa","year":"2001","unstructured":"Asakawa, A. et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology https:\/\/doi.org\/10.1053\/gast.2001.22158 (2001).","journal-title":"Gastroenterology"},{"key":"97440_CR4","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4518","author":"K Toshinai","year":"2001","unstructured":"Toshinai, K. et al. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem. Biophys. Res. Commun. https:\/\/doi.org\/10.1006\/bbrc.2001.4518 (2001).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"97440_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/35038090","author":"M Tschop","year":"2000","unstructured":"Tschop, M., Smiley, D. L. & Heiman, M. L. Ghrelin induces adiposity in rodents. Nature https:\/\/doi.org\/10.1038\/35038090 (2000).","journal-title":"Nature"},{"key":"97440_CR6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.25.14623","author":"O Gavrilova","year":"1999","unstructured":"Gavrilova, O. et al. Torpor in mice is induced by both leptin-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA. https:\/\/doi.org\/10.1073\/pnas.96.25.14623 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"97440_CR7","doi-asserted-by":"publisher","first-page":"227","DOI":"10.2337\/diabetes.50.2.227","volume":"50","author":"M Shintani","year":"2001","unstructured":"Shintani, M. et al. Rapid publication ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y\/Y1 receptor pathway. Diabetes 50, 227\u2013232 (2001).","journal-title":"Diabetes"},{"key":"97440_CR8","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.4212","author":"Y Date","year":"2001","unstructured":"Date, Y. et al. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem. Biophys. Res. Commun. https:\/\/doi.org\/10.1006\/bbrc.2000.4212 (2001).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"97440_CR9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00232.2006","author":"EF Gluck","year":"2006","unstructured":"Gluck, E. F., Stephens, N. & Swoap, S. J. Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway. Am. J. Physiol. Regul. Integr. Comp. Physiol. https:\/\/doi.org\/10.1152\/ajpregu.00232.2006 (2006).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"97440_CR10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903090106","author":"\u00c9 Szentirmai","year":"2009","unstructured":"Szentirmai, \u00c9., Kap\u00e1s, L., Sun, Y., Smith, R. G. & Krueger, J. M. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. Proc. Natl. Acad. Sci. USA https:\/\/doi.org\/10.1073\/pnas.0903090106 (2009).","journal-title":"Proc. Natl. Acad. 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