{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:09:39Z","timestamp":1778854179307,"version":"3.51.4"},"reference-count":79,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 BX001146"],"award-info":[{"award-number":["I01 BX001146"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD100580"],"award-info":[{"award-number":["R01 HD100580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD072754"],"award-info":[{"award-number":["R01 HD072754"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD082567"],"award-info":[{"award-number":["R01 HD082567"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000006","name":"Office of Naval Research","doi-asserted-by":"publisher","award":["N00014-13-1-0285"],"award-info":[{"award-number":["N00014-13-1-0285"]}],"id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NICHD","doi-asserted-by":"publisher","award":["P42 ES010337"],"award-info":[{"award-number":["P42 ES010337"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NICHD","doi-asserted-by":"publisher","award":["P50 HD012303"],"award-info":[{"award-number":["P50 HD012303"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NICHD","doi-asserted-by":"publisher","award":["K99\/R00 HD084759"],"award-info":[{"award-number":["K99\/R00 HD084759"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NICHD","doi-asserted-by":"publisher","award":["P30 CA023100"],"award-info":[{"award-number":["P30 CA023100"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NICHD","doi-asserted-by":"publisher","award":["P30 DK063491"],"award-info":[{"award-number":["P30 DK063491"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007911","name":"University of California, San Diego","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007917","name":"USDA Agricultural Research Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.molmet.2021.101431","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T22:06:06Z","timestamp":1640901966000},"page":"101431","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice"],"prefix":"10.1016","volume":"57","author":[{"given":"Jason D.","family":"Meadows","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-2115","authenticated-orcid":false,"given":"Shanna N.","family":"Lavalle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-1995","authenticated-orcid":false,"given":"Michael R.","family":"Hirschenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meera M.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duong","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-2583","authenticated-orcid":false,"given":"Alyssa","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Cassin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6122-8437","authenticated-orcid":false,"given":"Michael R.","family":"Gorman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9121-3164","authenticated-orcid":false,"given":"David K.","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-0410","authenticated-orcid":false,"given":"Pamela L.","family":"Mellon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-1369","authenticated-orcid":false,"given":"Hanne M.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.molmet.2021.101431_bib1","series-title":"Obesity and overweight (WHO fact sheet)","author":"World Health Organization","year":"2021"},{"issue":"17","key":"10.1016\/j.molmet.2021.101431_bib2","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1056\/NEJMoa021423","article-title":"Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults","volume":"348","author":"Calle","year":"2003","journal-title":"New England Journal of Medicine"},{"issue":"48","key":"10.1016\/j.molmet.2021.101431_bib3","doi-asserted-by":"crossref","first-page":"3560","DOI":"10.1093\/eurheartj\/ehv509","article-title":"Obesity and cardiovascular disease: friend or foe?","volume":"37","author":"Kim","year":"2016","journal-title":"European Heart Journal"},{"issue":"6","key":"10.1016\/j.molmet.2021.101431_bib4","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1242\/dmm.026609","article-title":"Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity","volume":"10","author":"Timper","year":"2017","journal-title":"Dis Model Mech"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cub.2013.01.048","article-title":"Circadian disruption leads to insulin resistance and obesity","volume":"23","author":"Shi","year":"2013","journal-title":"Current Biology"},{"issue":"5724","key":"10.1016\/j.molmet.2021.101431_bib6","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1126\/science.1108750","article-title":"Obesity and metabolic syndrome in circadian Clock mutant mice","volume":"308","author":"Turek","year":"2005","journal-title":"Science"},{"issue":"10","key":"10.1016\/j.molmet.2021.101431_bib7","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.cub.2012.03.038","article-title":"Social jetlag and obesity","volume":"22","author":"Roenneberg","year":"2012","journal-title":"Current Biology"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib8","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/ijo.2014.201","article-title":"Social jetlag, obesity and metabolic disorder: investigation in a cohort study","volume":"39","author":"Parsons","year":"2015","journal-title":"International Journal of Obesity"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib9","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/ijo.2012.229","article-title":"Timing of food intake predicts weight loss effectiveness","volume":"37","author":"Garaulet","year":"2013","journal-title":"International Journal of Obesity"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib10","doi-asserted-by":"crossref","first-page":"350","DOI":"10.30802\/AALAS-CM-19-000001","article-title":"Influence of daytime LED light exposure on circadian regulatory dynamics of metabolism and physiology in mice","volume":"69","author":"Dauchy","year":"2019","journal-title":"Comparative Medicine"},{"issue":"S1","key":"10.1016\/j.molmet.2021.101431_bib11","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1002\/oby.22807","article-title":"Metabolic implications of exposure to light at night: lessons from animal and human studies","volume":"28","author":"Fleury","year":"2020","journal-title":"Obesity"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib12","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.3390\/nu13051405","article-title":"Beneficial effects of early time-restricted feeding on metabolic diseases: importance of aligning food habits with the circadian clock","volume":"13","author":"Charlot","year":"2021","journal-title":"Nutrients"},{"issue":"7","key":"10.1016\/j.molmet.2021.101431_bib13","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1172\/JCI68035","article-title":"Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi-like features","volume":"123","author":"Bonnefond","year":"2013","journal-title":"Journal of Clinical Investigation"},{"issue":"7","key":"10.1016\/j.molmet.2021.101431_bib14","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1172\/JCI68016","article-title":"Rare variants in single-minded 1 (SIM1) are associated with severe obesity","volume":"123","author":"Ramachandrappa","year":"2013","journal-title":"Journal of Clinical Investigation"},{"issue":"Supplement_1","key":"10.1016\/j.molmet.2021.101431_bib15","doi-asserted-by":"crossref","DOI":"10.1210\/jendso\/bvaa046.159","article-title":"SAT-291 SIX3 is essential for hypothalamic and pituitary development","volume":"4","author":"Bando","year":"2020","journal-title":"Journal of the Endocrine Society"},{"issue":"12","key":"10.1016\/j.molmet.2021.101431_bib16","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1242\/dev.121.12.4045","article-title":"Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development","volume":"121","author":"Oliver","year":"1995","journal-title":"Development"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib17","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1242\/dev.077255","article-title":"Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development","volume":"139","author":"Anderson","year":"2012","journal-title":"Development"},{"issue":"3","key":"10.1016\/j.molmet.2021.101431_bib18","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/dvdy.20463","article-title":"Comparative analysis of Six 3 and Six 6 distribution in the developing and adult mouse brain","volume":"234","author":"Conte","year":"2005","journal-title":"Developmental Dynamics"},{"issue":"23","key":"10.1016\/j.molmet.2021.101431_bib19","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1242\/dev.132142","article-title":"Six3 dosage mediates the pathogenesis of holoprosencephaly","volume":"143","author":"Geng","year":"2016","journal-title":"Development"},{"issue":"3","key":"10.1016\/j.molmet.2021.101431_bib20","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1101\/gad.1059403","article-title":"Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development","volume":"17","author":"Lagutin","year":"2003","journal-title":"Genes & Development"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/humu.20056","article-title":"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations","volume":"24","author":"Dubourg","year":"2004","journal-title":"Human Mutation"},{"issue":"10","key":"10.1016\/j.molmet.2021.101431_bib22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/sj.ejhg.5200540","article-title":"A\u00a0new mutation in the six-domain of SIX3 gene causes holoprosencephaly","volume":"8","author":"Pasquier","year":"2000","journal-title":"European Journal of Human Genetics"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib23","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1136\/jmg.2004.023416","article-title":"First occurrence of aprosencephaly\/atelencephaly and holoprosencephaly in a family with a SIX3 gene mutation and phenotype\/genotype correlation in our series of SIX3 mutations","volume":"42","author":"Pasquier","year":"2005","journal-title":"Journal of Medical Genetics"},{"issue":"17","key":"10.1016\/j.molmet.2021.101431_bib24","doi-asserted-by":"crossref","first-page":"6457","DOI":"10.1523\/JNEUROSCI.5385-10.2011","article-title":"Development, maturation, and necessity of transcription factors in the mouse suprachiasmatic nucleus","volume":"31","author":"VanDunk","year":"2011","journal-title":"Journal of Neuroscience"},{"issue":"10","key":"10.1016\/j.molmet.2021.101431_bib25","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/jnr.24864","article-title":"The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice","volume":"99","author":"Hoffmann","year":"2021","journal-title":"Journal of Neuroscience Research"},{"issue":"24","key":"10.1016\/j.molmet.2021.101431_bib26","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1242\/dev.067470","article-title":"Six3 is required for ependymal cell maturation","volume":"138","author":"Lavado","year":"2011","journal-title":"Development"},{"issue":"14","key":"10.1016\/j.molmet.2021.101431_bib27","doi-asserted-by":"crossref","first-page":"dev165456","DOI":"10.1242\/dev.165456","article-title":"SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression","volume":"145","author":"Xu","year":"2018","journal-title":"Development"},{"issue":"3","key":"10.1016\/j.molmet.2021.101431_bib28","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41419-021-03552-8","article-title":"Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons","volume":"12","author":"Yang","year":"2021","journal-title":"Cell Death & Disease"},{"issue":"7","key":"10.1016\/j.molmet.2021.101431_bib29","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s12264-021-00698-5","article-title":"Homeobox gene Six3 is required for the differentiation of D2-type medium spiny neurons","volume":"37","author":"Song","year":"2021","journal-title":"Neurosci Bull"},{"issue":"Suppl 1","key":"10.1016\/j.molmet.2021.101431_bib30","article-title":"OR16-01 the expression of the homeodomain transcription factor SIX3 within kisspeptin neurons is necessary for reproduction in mice","volume":"4","author":"Lavalle","year":"2020","journal-title":"Journal of the Endocrine Society"},{"issue":"22","key":"10.1016\/j.molmet.2021.101431_bib31","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1038\/sj.emboj.7601398","article-title":"Six3 activation of Pax6 expression is essential for mammalian lens induction and specification","volume":"25","author":"Liu","year":"2006","journal-title":"The EMBO Journal"},{"key":"10.1016\/j.molmet.2021.101431_bib32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuroscience.2010.11.022","article-title":"Characterization of Kiss1 neurons using transgenic mouse models","volume":"173","author":"Cravo","year":"2011","journal-title":"Neuroscience"},{"issue":"3","key":"10.1016\/j.molmet.2021.101431_bib33","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1177\/0748730411402810","article-title":"Cyclic AMP signaling control of action potential firing rate and molecular circadian pacemaking in the suprachiasmatic nucleus","volume":"26","author":"Atkinson","year":"2011","journal-title":"Journal of Biological Rhythms"},{"key":"10.1016\/j.molmet.2021.101431_bib34","article-title":"Determination of reproductive competence by confirming pubertal onset and performing a fertility assay in mice and rats","volume":"140","author":"Hoffmann","year":"2018","journal-title":"Journal of Visualized Experiments"},{"issue":"10","key":"10.1016\/j.molmet.2021.101431_bib35","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1210\/en.2014-1277","article-title":"Heterozygous deletion of ventral anterior homeobox (vax1) causes subfertility in mice","volume":"155","author":"Hoffmann","year":"2014","journal-title":"Endocrinology"},{"issue":"2","key":"10.1016\/j.molmet.2021.101431_bib36","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1523\/JNEUROSCI.1688-10.2011","article-title":"Hypothalamic dysregulation and infertility in mice lacking the homeodomain protein Six6","volume":"31","author":"Larder","year":"2011","journal-title":"Journal of Neuroscience"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib37","doi-asserted-by":"crossref","first-page":"bqab023","DOI":"10.1210\/endocr\/bqab023","article-title":"Growth hormone pulses and liver gene expression are differentially regulated by the circadian clock gene Bmal1","volume":"162","author":"Schoeller","year":"2021","journal-title":"Endocrinology"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib38","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0022-5193(78)90022-X","article-title":"The chi square periodogram: its utility for analysis of circadian rhythms","volume":"72","author":"Sokolove","year":"1978","journal-title":"Journal of Theoretical Biology"},{"issue":"15","key":"10.1016\/j.molmet.2021.101431_bib40","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1073\/pnas.0308709101","article-title":"PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues","volume":"101","author":"Yoo","year":"2004","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"2","key":"10.1016\/j.molmet.2021.101431_bib41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0170904","article-title":"Potent effects of flavonoid nobiletin on amplitude, period, and phase of the circadian clock rhythm in PER2::LUCIFERASE mouse embryonic fibroblasts","volume":"12","author":"Shinozaki","year":"2017","journal-title":"PLoS One"},{"issue":"11","key":"10.1016\/j.molmet.2021.101431_bib42","doi-asserted-by":"crossref","first-page":"8709","DOI":"10.1007\/s12035-018-1013-0","article-title":"Haploinsufficiency of SIX3 abolishes male reproductive behavior rhrough disrupted olfactory development, and impairs female fertility through disrupted GnRH neuron migration","volume":"55","author":"Pandolfi","year":"2018","journal-title":"Molecular Neurobiology"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib43","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1159\/000497791","article-title":"Differential CRE expression in lhrh-cre and GnRH-cre alleles and the impact on fertility in otx2-flox mice","volume":"108","author":"Hoffmann","year":"2019","journal-title":"Neuroendocrinology"},{"key":"10.1016\/j.molmet.2021.101431_bib44","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.mce.2017.09.004","article-title":"Transcriptional interaction between cFOS and the homeodomain-binding transcription factor VAX1 on the GnRH promoter controls Gnrh1 expression levels in a GnRH neuron maturation specific manner","volume":"461","author":"Hoffmann","year":"2018","journal-title":"Molecular and Cellular Endocrinology"},{"key":"10.1016\/j.molmet.2021.101431_bib45","article-title":"Wheel running in the wild","volume":"281","author":"Meijer","year":"2014","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"issue":"3","key":"10.1016\/j.molmet.2021.101431_bib46","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.neubiorev.2011.12.012","article-title":"The use of a running wheel to measure activity in rodents: relationship to energy balance, general activity, and reward","volume":"36","author":"Novak","year":"2012","journal-title":"Neuroscience & Biobehavioral Reviews"},{"issue":"2","key":"10.1016\/j.molmet.2021.101431_bib47","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1210\/en.2015-1645","article-title":"Conditional deletion of Bmal1 in ovarian theca cells disrupts ovulation in female mice","volume":"157","author":"Mereness","year":"2016","journal-title":"Endocrinology"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib48","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1177\/0748730414549767","article-title":"Disrupted reproduction, estrous cycle, and circadian rhythms in female mice deficient in vasoactive intestinal peptide","volume":"29","author":"Loh","year":"2014","journal-title":"Journal of Biological Rhythms"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib49","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1677\/JOE-07-0102","article-title":"Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis","volume":"194","author":"Lacombe","year":"2007","journal-title":"Journal of Endocrinology"},{"issue":"7","key":"10.1016\/j.molmet.2021.101431_bib50","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1093\/jn\/131.7.2067","article-title":"Differences between humans and mice in efficacy of the body fat lowering effect of conjugated linoleic acid: role of metabolic rate","volume":"131","author":"Terpstra","year":"2001","journal-title":"Journal of Nutrition"},{"issue":"2","key":"10.1016\/j.molmet.2021.101431_bib51","doi-asserted-by":"crossref","first-page":"R344","DOI":"10.1152\/ajpregu.00667.2007","article-title":"Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling","volume":"294","author":"Bechtold","year":"2008","journal-title":"American Journal of Physiology - Regulatory, Integrative and Comparative Physiology"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib52","doi-asserted-by":"crossref","first-page":"229","DOI":"10.5483\/BMBRep.2015.48.4.272","article-title":"Network of hypothalamic neurons that control appetite","volume":"48","author":"Sohn","year":"2015","journal-title":"BMB Rep"},{"key":"10.1016\/j.molmet.2021.101431_bib53","doi-asserted-by":"crossref","first-page":"170555","DOI":"10.1016\/j.peptides.2021.170555","article-title":"Arginine vasopressin: direct and indirect action on metabolism","volume":"142","author":"Yoshimura","year":"2021","journal-title":"Peptides"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib54","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1038\/s41467-020-17578-7","article-title":"Paraventricular hypothalamus mediates diurnal rhythm of metabolism","volume":"11","author":"Kim","year":"2020","journal-title":"Nature Communications"},{"issue":"5487","key":"10.1016\/j.molmet.2021.101431_bib55","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1126\/science.289.5487.2122","article-title":"Role of brain insulin receptor in control of body weight and reproduction","volume":"289","author":"Br\u00fcning","year":"2000","journal-title":"Science"},{"issue":"5","key":"10.1016\/j.molmet.2021.101431_bib56","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s00018-012-1095-1","article-title":"Leptin signaling and circuits in puberty and fertility","volume":"70","author":"Elias","year":"2013","journal-title":"Cellular and Molecular Life Sciences"},{"issue":"6","key":"10.1016\/j.molmet.2021.101431_bib57","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1210\/en.2008-1693","article-title":"Leptin indirectly regulates gonadotropin-releasing hormone neuronal function","volume":"150","author":"Quennell","year":"2009","journal-title":"Endocrinology"},{"issue":"14","key":"10.1016\/j.molmet.2021.101431_bib58","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1523\/JNEUROSCI.3138-16.2017","article-title":"Leptin signaling in AgRP neurons modulates puberty onset and adult fertility in mice","volume":"37","author":"Egan","year":"2017","journal-title":"Journal of Neuroscience"},{"issue":"12","key":"10.1016\/j.molmet.2021.101431_bib59","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1172\/JCI11941","article-title":"Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth","volume":"107","author":"Low","year":"2001","journal-title":"Journal of Clinical Investigation"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib60","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1210\/endo-125-1-357","article-title":"Sexual dimorphism and testosterone-dependent regulation of somatostatin gene expression in the periventricular nucleus of the rat brain","volume":"125","author":"Chowen-Breed","year":"1989","journal-title":"Endocrinology"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib61","first-page":"342","article-title":"Somatostatin messenger RNA in hypothalamic neurons is increased by testosterone through activation of androgen receptors and not by aromatization to estradiol","volume":"52","author":"Argente","year":"1990","journal-title":"Neuroendocrinology"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/1471-2164-8-353","article-title":"Gene expression profiling of long-lived dwarf mice: longevity-associated genes and relationships with diet, gender and aging","volume":"8","author":"Swindell","year":"2007","journal-title":"BMC Genomics"},{"issue":"21","key":"10.1016\/j.molmet.2021.101431_bib63","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1128\/MCB.00171-12","article-title":"Insulin-like growth factor 1 mediates negative feedback to somatotroph GH expression via POU1F1\/CREB binding protein interactions","volume":"32","author":"Romero","year":"2012","journal-title":"Molecular and Cellular Biology"},{"issue":"11","key":"10.1016\/j.molmet.2021.101431_bib64","doi-asserted-by":"crossref","first-page":"4762","DOI":"10.1210\/endo.142.11.8478","article-title":"Liver-derived IGF-I regulates GH secretion at the pituitary level in mice","volume":"142","author":"Wallenius","year":"2001","journal-title":"Endocrinology"},{"issue":"1\u20132","key":"10.1016\/j.molmet.2021.101431_bib65","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.mce.2013.09.004","article-title":"Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications","volume":"386","author":"Kopchick","year":"2014","journal-title":"Molecular and Cellular Endocrinology"},{"issue":"8","key":"10.1016\/j.molmet.2021.101431_bib66","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1210\/me.2007-0549","article-title":"Sex-specific early growth hormone response genes in rat liver","volume":"22","author":"Wauthier","year":"2008","journal-title":"Molecular Endocrinology"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib67","doi-asserted-by":"crossref","first-page":"12563","DOI":"10.1111\/jne.12563","article-title":"Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high-fat diet","volume":"30","author":"Luo","year":"2018","journal-title":"Journal of Neuroendocrinology"},{"key":"10.1016\/j.molmet.2021.101431_bib68","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fnins.2013.00185","article-title":"Circadian adaptations to meal timing: neuroendocrine mechanisms","volume":"7","author":"Patton","year":"2013","journal-title":"Frontiers in Neuroscience"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib69","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1249\/JES.0000000000000207","article-title":"A\u00a0time to eat and a time to exercise","volume":"48","author":"Parr","year":"2020","journal-title":"Exercise and Sport Sciences Reviews"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib70","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/s42003-021-02239-2","article-title":"Timed daily exercise remodels circadian rhythms in mice","volume":"4","author":"Hughes","year":"2021","journal-title":"Commun Biol"},{"issue":"2","key":"10.1016\/j.molmet.2021.101431_bib71","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1096\/fj.08-113191","article-title":"Circadian clock and output genes are rhythmically expressed in extratesticular ducts and accessory organs of mice","volume":"23","author":"Bebas","year":"2009","journal-title":"The FASEB Journal"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib72","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/0748730407311254","article-title":"The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice","volume":"23","author":"Alvarez","year":"2008","journal-title":"Journal of Biological Rhythms"},{"issue":"4","key":"10.1016\/j.molmet.2021.101431_bib73","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1177\/0748730420925573","article-title":"Reduced VIP expression affects circadian clock function in VIP-IRES-CRE mice (JAX 010908)","volume":"35","author":"Joye","year":"2020","journal-title":"Journal of Biological Rhythms"},{"issue":"2","key":"10.1016\/j.molmet.2021.101431_bib74","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1007\/s12035-019-01781-9","article-title":"The homeodomain transcription factors Vax1 and Six6 are required for SCN development and function","volume":"57","author":"Pandolfi","year":"2020","journal-title":"Molecular Neurobiology"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib75","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1534-5807(03)00399-X","article-title":"Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice","volume":"6","author":"Branda","year":"2004","journal-title":"Developmental Cell"},{"issue":"25","key":"10.1016\/j.molmet.2021.101431_bib76","doi-asserted-by":"crossref","first-page":"13702","DOI":"10.1073\/pnas.240471297","article-title":"Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids","volume":"97","author":"Schmidt","year":"2000","journal-title":"Proceedings of the National Academy of Sciences of the U S A"},{"issue":"1","key":"10.1016\/j.molmet.2021.101431_bib77","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/gene.20183","article-title":"Synapsin I Cre transgene expression in male mice produces germline recombination in progeny","volume":"44","author":"Rempe","year":"2006","journal-title":"Genesis"},{"issue":"8","key":"10.1016\/j.molmet.2021.101431_bib78","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/dvg.20226","article-title":"Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre\/loxP mediated recombination in the nervous system, kidney, and somite-derived tissues","volume":"44","author":"Dubois","year":"2006","journal-title":"Genesis"},{"issue":"8","key":"10.1016\/j.molmet.2021.101431_bib79","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s13238-020-00705-x","article-title":"Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity","volume":"11","author":"Ho","year":"2020","journal-title":"Protein Cell"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877821002891?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877821002891?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:21:22Z","timestamp":1778851282000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877821002891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":79,"alternative-id":["S2212877821002891"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2021.101431","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2021.101431","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"101431"}}