{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:38:08Z","timestamp":1793252288270,"version":"4.5.0"},"reference-count":78,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"528","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA163890"],"award-info":[{"award-number":["CA163890"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA194496"],"award-info":[{"award-number":["CA194496"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA127731"],"award-info":[{"award-number":["CA127731"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX003725"],"award-info":[{"award-number":["BX003725"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010470","name":"Gillson Longenbaugh Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK110439"],"award-info":[{"award-number":["DK110439"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK107444"],"award-info":[{"award-number":["DK107444"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK074970"],"award-info":[{"award-number":["DK074970"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dialysis Clinic, Inc","award":["RF#C-3937"],"award-info":[{"award-number":["RF#C-3937"]}]},{"name":"Gillson-Longenbaugh Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2020,1,29]]},"abstract":"<jats:p>Human obesity has become a global health epidemic, with few safe and effective pharmacological therapies currently available. The systemic loss of ovarian estradiol (E2) in women after menopause greatly increases the risk of obesity and metabolic dysfunction, revealing the critical role of E2 in this setting. The salutary effects of E2 are traditionally attributed to the classical estrogen receptors ER\u03b1 and ER\u03b2, with the contribution of the G protein\u2013coupled estrogen receptor (GPER) still largely unknown. Here, we used ovariectomy- and diet-induced obesity (DIO) mouse models to evaluate the preclinical activity of GPER-selective small-molecule agonist G-1 (also called Tespria) against obesity and metabolic dysfunction. G-1 treatment of ovariectomized female mice (a model of postmenopausal obesity) reduced body weight and improved glucose homeostasis without changes in food intake, fuel source usage, or locomotor activity. G-1\u2013treated female mice also exhibited increased energy expenditure, lower body fat content, and reduced fasting cholesterol, glucose, insulin, and inflammatory markers but did not display feminizing effects on the uterus (imbibition) or beneficial effects on bone health. G-1 treatment of DIO male mice did not elicit weight loss but prevented further weight gain and improved glucose tolerance, indicating that G-1 improved glucose homeostasis independently of its antiobesity effects. However, in ovariectomized DIO female mice, G-1 continued to elicit weight loss, reflecting possible sex differences in the mechanisms of G-1 action. In conclusion, this work demonstrates that GPER-selective agonism is a viable therapeutic approach against obesity, diabetes, and associated metabolic abnormalities in multiple preclinical male and female models.<\/jats:p>","DOI":"10.1126\/scitranslmed.aau5956","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:05:18Z","timestamp":1580342718000},"source":"Crossref","is-referenced-by-count":100,"title":["Preclinical efficacy of the GPER-selective agonist G-1 in mouse models of obesity and diabetes"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-0743","authenticated-orcid":true,"given":"Geetanjali","family":"Sharma","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-652X","authenticated-orcid":true,"given":"Chelin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela I.","family":"Staquicini","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA."},{"name":"Rutgers Cancer Institute of New Jersey, Newark, NJ 07103, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Brigman","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-262X","authenticated-orcid":true,"given":"Meilian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."},{"name":"Center of Biomedical Research Excellence in Autophagy, Inflammation and Metabolism, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Mauvais-Jarvis","sequence":"additional","affiliation":[{"name":"Diabetes Discovery and Sex-Based Medicine Laboratory, Section of Endocrinology and Metabolism, Department of Medicine, Tulane University Health Sciences Center, School of Medicine, New Orleans, LA 70112, USA."},{"name":"Section of Endocrinology, Southeast Louisiana Veterans Administration Health Care System, New Orleans, LA 70112, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Pasqualini","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA."},{"name":"Rutgers Cancer Institute of New Jersey, Newark, NJ 07103, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih","family":"Arap","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, Newark, NJ 07103, USA."},{"name":"Division of Hematology\/Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9133-2892","authenticated-orcid":true,"given":"Jeffrey B.","family":"Arterburn","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, 88003, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-5056","authenticated-orcid":true,"given":"Helen J.","family":"Hathaway","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."},{"name":"University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-8302","authenticated-orcid":true,"given":"Eric R.","family":"Prossnitz","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."},{"name":"Center of Biomedical Research Excellence in Autophagy, Inflammation and Metabolism, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."},{"name":"University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666151109103147"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-016-9333-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.6458"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2017.08.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1048"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002621"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31271-1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12839"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2010.184"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-018-0300-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2010.02237.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27987"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2014.02.002"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-015-0033-y"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106943"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1699-6"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100518"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-70178-3_20"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2017.02.012"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3127-9_38"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2015.02.003"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.01.001"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aag0240"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1357"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2014.02.004"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio775"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.168"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.07.002"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009712"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2017.03.005"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2019.10.009"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.190892"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-0091"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0623"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep34302"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-6009(91)90108-C"},{"key":"e_1_3_2_39_2","first-page":"667","article-title":"Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: The Baltimore Longitudinal Study on Aging","volume":"16","author":"Seidell J. C.","year":"1992","unstructured":"J. C. Seidell, D. C. Muller, J. D. Sorkin, R. Andres, Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: The Baltimore Longitudinal Study on Aging. Int. J. Obes. Relat. Metab. Disord. 16, 667\u2013674 (1992).","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2008.229"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90760.2008"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071812-161156"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0203"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.2007.S143"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.220"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.23.12729"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00504.2009"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2015.06.014"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.102"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12471"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1079\/PNS2004408"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2015.00136"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-38259"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/757461"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1300-4"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2013.12.009"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00733.2007"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-1339"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920309787315239"},{"key":"e_1_3_2_60_2","first-page":"1770","article-title":"Leptin in postmenopausal women: Influence of hormone therapy, insulin, and fat distribution","volume":"85","author":"Gower B. A.","year":"2000","unstructured":"B. A. Gower, T. R. Nagy, M. I. Goran, A. Smith, E. Kent, Leptin in postmenopausal women: Influence of hormone therapy, insulin, and fat distribution. J. Clin. Endocrinol. Metab. 85, 1770\u20131775 (2000).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00492.2012"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.023"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00121.2013"},{"key":"e_1_3_2_64_2","first-page":"2511","article-title":"Bioenergetic profile experiment using C2C12 myoblast cells","volume":"2010","author":"Nicholls D. G.","year":"2010","unstructured":"D. G. Nicholls, V. M. Darley-Usmar, M. Wu, P. B. Jensen, G. W. Rogers, D. A. Ferrick, Bioenergetic profile experiment using C2C12 myoblast cells. J. Vis. Exp. 2010, 2511 (2010).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.05.040"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092358"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0001"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2011.07.014"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-017-0151-9"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.06.023"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e31828d8e3b"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03471.x"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1989"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00638.2011"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1510503"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11468"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep07564"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1039\/c001307b"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.018"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1126\/scitranslmed.aau5956","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aau5956","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T17:36:37Z","timestamp":1705426597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.aau5956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,29]]},"references-count":78,"journal-issue":{"issue":"528","published-print":{"date-parts":[[2020,1,29]]}},"alternative-id":["10.1126\/scitranslmed.aau5956"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.aau5956","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,29]]},"article-number":"eaau5956"}}