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Adv."],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:p>\n                    Endotherms use complex internal mechanisms to maintain a steady body temperature, whereas ectotherms rely on environmental factors and behaviors for thermoregulation. Certain ectothermic animals, like some lizards, can also physiologically regulate their body temperature to some extent, with interspecies variations in thermoregulatory capacity under low-temperature conditions. However, the molecular mechanisms underlying this physiological regulation have remained unclear since its discovery about 80 years ago. Here, we reveal that the hepatic expression of constitutively active glucagon receptor (GCGR) in lizards, particularly in iguana, correlated with their thermoregulatory capacity when kept at low temperatures. When\n                    <jats:italic toggle=\"yes\">Pogona vitticeps<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Phrynocephalus vlangalii<\/jats:italic>\n                    with thermoregulatory capacity were treated with short hairpin RNA\u2013\n                    <jats:italic toggle=\"yes\">GCGR<\/jats:italic>\n                    or GCGR antagonist, their body temperatures dropped, and the expression of genes related to energy metabolism and respiratory metabolic rate was down-regulated. In contrast,\n                    <jats:italic toggle=\"yes\">Eremias argus<\/jats:italic>\n                    , lacking thermoregulatory ability, revealed low hepatic GCGR expression. Overexpression of\n                    <jats:italic toggle=\"yes\">P. vitticeps GCGR<\/jats:italic>\n                    (pv\n                    <jats:italic toggle=\"yes\">GCGR<\/jats:italic>\n                    ) in the liver of\n                    <jats:italic toggle=\"yes\">E. argus<\/jats:italic>\n                    increased body temperature and enhanced energy metabolism. Furthermore, in mice with reduced thermoregulatory ability by chlorpromazine administration, overexpression of constitutively active GCGR ligand-independently increased body temperature under cold conditions. In conclusion, constitutively active GCGR drives the physiological thermoregulation in lizards, and our study offered previously unidentified insights into expression regulation of constitutively active GPCR into physiological adaptations responding to environmental changes.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb8744","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:58:41Z","timestamp":1787335121000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Constitutively active glucagon receptor (GCGR) physiologically regulates body temperature in lizards"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5253-3211","authenticated-orcid":true,"given":"Songsong","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Biodiversity and Biotechnology, State Key Laboratory of Microbial Technology, College of Life Sciences, Nanjing Normal University, Nanjing, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Ren","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Biodiversity and Biotechnology, State Key Laboratory of Microbial Technology, College of Life Sciences, Nanjing Normal University, Nanjing, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Lai","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Biodiversity and Biotechnology, State Key Laboratory of Microbial Technology, College of Life Sciences, Nanjing Normal University, Nanjing, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangying","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of High Altitude Medicine, Center for High Altitude Medicine, College of Life Sciences, West China Hospital, Sichuan University, Chengdu, Sichuan, PR 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