{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:34:02Z","timestamp":1781278442124,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Daily torpor is an active hypothermic phenomenon that is observed in some mammals and birds during fasting. A decrease in blood pressure has also been observed in torpor; however, there remains a lack of knowledge of the underlying mechanism. We have previously reported that ghrelin, an orexigenic hormone, has a hypothermic effect and is essential for the induction and maintenance of torpor. It is also known that the ghrelin secretion is enhanced during fasting and that ghrelin receptors are distributed in the cardiovascular system. Therefore, this study was conducted to test the hypothesis that ghrelin is actively involved in the regulation of blood pressure during torpor induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male wild-type and ghrelin gene-deficient mice were generated by homologous recombination as previously reported. Mice, 10 weeks old, were included in this study and housed five per cage. The mice were maintained on a 12-h light\/dark cycle (lights on from 7:00 to 19:00) with access to food and water ad libitum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The continuous measurement of blood pressure using a telemetry system showed that induction of torpor by fasting did not decrease blood pressure in ghrelin gene-deficient mice. The analysis of heart rate variability revealed that sympathetic nerve activity was predominant in ghrelin-deficient mice during fasting. Furthermore, these features were cancelled by administration of a ghrelin receptor agonist and were comparable to those in wild-type mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In this study, we showed that blood pressure was elevated in <jats:italic>ghrl<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice and that the blood pressure rhythm was abnormal. Furthermore, we showed that the ghrelin gene deficiency does not cause sufficient blood pressure reduction upon entry into the torpor, and that the administration of the ghrelin receptor agonist, GHRP-6, causes blood pressure reduction associated with torpor. Thus, we have shown for the first time that the active role of ghrelin is essential for active blood pressure reduction associated with torpor, and that this action is mediated by the inhibition of sympathetic nerve activity by ghrelin.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1487028","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T11:45:03Z","timestamp":1728560703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Ghrelin is essential for lowering blood pressure during torpor"],"prefix":"10.3389","volume":"15","author":[{"given":"Kazuma","family":"Matsui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanae","family":"Oishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayasu","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17954","DOI":"10.1038\/s41598-021-97440-y","article-title":"Thermoregulatory role of ghrelin in the induction of torpor under a restricted feeding condition","volume":"11","author":"Sato","year":"2021","journal-title":"Sci Rep"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/35051587","article-title":"A role for ghrelin in the central regulation of feeding","volume":"409","author":"Nakazato","year":"2001","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/35038090","article-title":"Ghrelin induces adiposity in rodents","volume":"407","author":"Tschop","year":"2000","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.22158","article-title":"Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin","volume":"120","author":"Asakawa","year":"2001","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4518","article-title":"Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration","volume":"281","author":"Toshinai","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1040","article-title":"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","volume":"151","author":"Ariyasu","year":"2010","journal-title":"Endocrinology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0174","article-title":"Molecular forms of hypothalamic ghrelin and its regulation by fasting and 2-deoxy-D-glucose administration","volume":"146","author":"Sato","year":"2005","journal-title":"Endocrinology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3721-05.2006","article-title":"The full expression of fasting-induced torpor requires \u03b23-adrenergic receptor signaling","volume":"26","author":"Swoap","year":"2006","journal-title":"J Neurosci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2008.09.023","article-title":"Energetics of fasting heterothermia in TRPV1-KO and wild type mice","volume":"96","author":"Kanizsai","year":"2009","journal-title":"Physiol Behav"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1977.42.3.420","article-title":"Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia","volume":"42","author":"Tempel","year":"1977","journal-title":"J Appl Physiol Respair Environ Exerc Physiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00131.2009","article-title":"Cardiovascular changes during daily torpor in the laboratory mouse","volume":"297","author":"Swoap","year":"2009","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-835367","article-title":"Ghrelin and synthetic growth hormone secretagogues are cardioactive molecules with identities and differences","volume":"4","author":"Benso","year":"2004","journal-title":"Semin Vasc Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2988","DOI":"10.1210\/jcem.87.6.8739","article-title":"The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans","volume":"87","author":"Gnanapavan","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704228","article-title":"125I-His(9)]-Ghrelin, a novel radioligand for localizing GHS orphan receptors in human and rat tissue; up-regulation of receptors with atherosclerosis","volume":"134","author":"Katugampola","year":"2001","journal-title":"Br J Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1586\/eem.09.7","article-title":"Therapeutic potential of ghrelin in cardiac diseases","volume":"4","author":"Kishimoto","year":"2009","journal-title":"Expert Rev Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/138161212803216906","article-title":"The growth hormone secretagogue receptor (Ghs-R)","volume":"18","author":"Laviano","year":"2012","journal-title":"Curr Pharm Des"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.5.r1483","article-title":"Hemodynamic and hormonal effects of human ghrelin in healthy volunteers","volume":"280","author":"Nagaya","year":"2001","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.12.8115","article-title":"Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure","volume":"86","author":"Nagaya","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000149746.62908.BB","article-title":"Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure","volume":"110","author":"Nagaya","year":"2004","journal-title":"Circulation"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00643.2007","article-title":"Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction","volume":"294","author":"Soeki","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/biology11081190","article-title":"Effect of ghrelin on the cardiovascular system","volume":"11","author":"Hosoda","year":"2022","journal-title":"Biol (Basel)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s11906-015-0622-5","article-title":"Ghrelin and blood pressure regulation","volume":"18","author":"Mao","year":"2016","journal-title":"Curr Hypertens Rep"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200206000-00001","article-title":"Vasodilatory effect of ghrelin, an endogenous peptide from the stomach","volume":"39","author":"Okumura","year":"2002","journal-title":"J\u00a0Cardiovasc Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart\u00a0rate\u00a0variability. Standards of measurement, physiological interpretation, and\u00a0clinical use","volume":"17","author":"Malik","year":"1996","journal-title":"Eur Heart J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.regpep.2007.09.010","article-title":"Ghrelin deficiency does not influence feeding performance","volume":"145","author":"Sato","year":"2008","journal-title":"Regul Pept"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.23.22.7973-7981.2003","article-title":"Deletion of ghrelin impairs neither growth nor appetite","volume":"23","author":"Sun","year":"2003","journal-title":"Mol Cell Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0789","article-title":"Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans","volume":"176","author":"Zhang","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000122803.91559.55","article-title":"Ghrelin acts at the nucleus of the solitary tract to decrease arterial pressure in rats","volume":"43","author":"Lin","year":"2004","journal-title":"Hypertension"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ng1504","article-title":"System-level identification of transcriptional circuits underlying mammalian circadian clocks","volume":"37","author":"Ueda","year":"2005","journal-title":"Nat Genet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.11.024","article-title":"Circadian clock-mediated regulation of blood pressure","volume":"119","author":"Douma","year":"2018","journal-title":"Free Radic Biol Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.orcp.2013.10.002","article-title":"Physiological roles of ghrelin on obesity","volume":"8","author":"Sato","year":"2014","journal-title":"Obes Res Clin Pract"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvr134","article-title":"Structure, regulation and function of ghrelin","volume":"151","author":"Sato","year":"2012","journal-title":"J Biochem"},{"key":"B34","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1152\/physrev.00012.2004","article-title":"Ghrelin: structure and function","volume":"85","author":"Kojima","year":"2005","journal-title":"Physiol Rev"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.peptides.2014.09.015","article-title":"Effect of ghrelin on autonomic activity in healthy volunteers","volume":"62","author":"Soeki","year":"2014","journal-title":"Peptides (NY)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5803","DOI":"10.1038\/s41467-024-49996-2","article-title":"Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation","volume":"15","author":"Mohr","year":"2024","journal-title":"Nat Commun"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1487028\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T11:45:06Z","timestamp":1728560706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1487028\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,10]]},"references-count":36,"alternative-id":["10.3389\/fendo.2024.1487028"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2024.1487028","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,10]]},"article-number":"1487028"}}