{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:07:14Z","timestamp":1767834434765,"version":"3.49.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H04682"],"award-info":[{"award-number":["15H04682"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K19517"],"award-info":[{"award-number":["15K19517"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-\/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.<\/jats:p>","DOI":"10.1093\/gerona\/gly282","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T02:54:05Z","timestamp":1545015245000},"page":"1042-1049","source":"Crossref","is-referenced-by-count":7,"title":["NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning"],"prefix":"10.1093","volume":"75","author":[{"given":"Seongjoon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erkhembayar","family":"Nayantai","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshimitsu","family":"Komatsu","sequence":"first","affiliation":[{"name":"Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isao","family":"Shimokawa","sequence":"first","affiliation":[{"name":"Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"2020052208494639500_CIT0001","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.plipres.2009.05.001","article-title":"Lipolysis and lipid mobilization in human adipose tissue","volume":"48","author":"Lafontan","year":"2009","journal-title":"Prog Lipid Res"},{"key":"2020052208494639500_CIT0002","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S0140-6736(09)60318-4","article-title":"Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies","volume":"373","author":"Lewington","year":"2009","journal-title":"Lancet"},{"key":"2020052208494639500_CIT0003","doi-asserted-by":"crossref","first-page":"17576","DOI":"10.1073\/pnas.0909055106","article-title":"aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues","volume":"106","author":"Mao","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020052208494639500_CIT0004","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1552-6909.2007.00180.x","article-title":"Postmenopausal women and the health consequences of obesity","volume":"36","author":"Dennis","year":"2007","journal-title":"J Obstet Gynecol Neonatal Nurs"},{"key":"2020052208494639500_CIT0005","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0092-8674(03)01081-X","article-title":"Obesity wars: molecular progress confronts an expanding epidemic","volume":"116","author":"Flier","year":"2004","journal-title":"Cell"},{"key":"2020052208494639500_CIT0006","doi-asserted-by":"crossref","first-page":"452524","DOI":"10.1155\/2012\/452524","article-title":"Diet-induced obesity in mice overexpressing neuropeptide y in noradrenergic neurons","volume":"2012","author":"Ruohonen","year":"2012","journal-title":"Int J Pept"},{"key":"2020052208494639500_CIT0007","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0959-4388(92)90144-A","article-title":"Hypothalamic neuropeptide Y regulation of feeding and energy metabolism","volume":"2","author":"Billington","year":"1992","journal-title":"Curr Opin Neurobiol"},{"key":"2020052208494639500_CIT0008","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.cmet.2011.02.019","article-title":"Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity","volume":"13","author":"Chao","year":"2011","journal-title":"Cell Metab"},{"key":"2020052208494639500_CIT0009","doi-asserted-by":"crossref","first-page":"7154","DOI":"10.1073\/pnas.0510320103","article-title":"A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice","volume":"103","author":"Ishihara","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020052208494639500_CIT0010","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.tem.2006.12.001","article-title":"Estrogen receptors in neuropeptide Y neurons: at the crossroads of feeding and reproduction","volume":"18","author":"Acosta-Martinez","year":"2007","journal-title":"Trends Endocrinol Metab"},{"key":"2020052208494639500_CIT0011","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00026.2006","article-title":"Estrogen receptors: how do they signal and what are their targets","volume":"87","author":"Heldring","year":"2007","journal-title":"Physiol Rev"},{"key":"2020052208494639500_CIT0012","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0960-0760(95)00084-D","article-title":"Antiestrogens: mechanisms and actions in target cells","volume":"53","author":"Katzenellenbogen","year":"1995","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020052208494639500_CIT0013","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1080\/10715760600952851","article-title":"Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens","volume":"40","author":"Vi\u00f1a","year":"2006","journal-title":"Free Radic Res"},{"key":"2020052208494639500_CIT0014","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1097\/00075197-200111000-00008","article-title":"Oestrogen and sex influence on muscle damage and inflammation: evidence from animal models","volume":"4","author":"Tiidus","year":"2001","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"2020052208494639500_CIT0015","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00394-011-0266-4","article-title":"Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance","volume":"51","author":"Stubbins","year":"2012","journal-title":"Eur J Nutr"},{"key":"2020052208494639500_CIT0016","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.rcl.2010.02.014","article-title":"Physiology of bone loss","volume":"48","author":"Clarke","year":"2010","journal-title":"Radiol Clin North Am"},{"key":"2020052208494639500_CIT0017","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1749-6632.2010.05526.x","article-title":"Reproductive aging, menopause, and health outcomes","volume":"1204","author":"Pinkerton","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"2020052208494639500_CIT0018","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1096\/fj.14-258384","article-title":"NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism","volume":"28","author":"Park","year":"2014","journal-title":"FASEB J"},{"key":"2020052208494639500_CIT0019","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2014.03.031","article-title":"Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK","volume":"20","author":"Mart\u00ednez de Morentin","year":"2014","journal-title":"Cell Metab"},{"key":"2020052208494639500_CIT0020","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1098\/rstb.2006.1860","article-title":"Modulation of appetite by gonadal steroid hormones","volume":"361","author":"Asarian","year":"2006","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2020052208494639500_CIT0021","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1210\/en.2009-1198","article-title":"Neuropeptide Y directly inhibits neuronal activity in a subpopulation of gonadotropin-releasing hormone-1 neurons via Y1 receptors","volume":"151","author":"Klenke","year":"2010","journal-title":"Endocrinology"},{"key":"2020052208494639500_CIT0022","doi-asserted-by":"crossref","DOI":"10.1002\/mnfr.201600574","article-title":"Metabolic programming of a beige adipocyte phenotype by genistein","volume":"61","author":"Aziz","year":"2017","journal-title":"Mol Nutr Food Res"},{"key":"2020052208494639500_CIT0023","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1292\/jvms.13-0359","article-title":"Induction of beige-like adipocytes in 3T3-L1 cells","volume":"76","author":"Asano","year":"2014","journal-title":"J Vet Med Sci"},{"key":"2020052208494639500_CIT0024","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.molmed.2006.07.004","article-title":"Estrogen receptors: new players in diabetes mellitus","volume":"12","author":"Barros","year":"2006","journal-title":"Trends Mol Med"},{"key":"2020052208494639500_CIT0025","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/jcb.22553","article-title":"17beta-estradiol supplementation attenuates ovariectomy-induced increases in ATGL signaling and reduced perilipin expression in visceral adipose tissue","volume":"110","author":"Wohlers","year":"2010","journal-title":"J Cell Biochem"},{"key":"2020052208494639500_CIT0026","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/ijo.2012.71","article-title":"Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice","volume":"37","author":"Zengin","year":"2013","journal-title":"Int J Obes (Lond)"},{"key":"2020052208494639500_CIT0027","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/ijo.2010.124","article-title":"Estrogen inhibits NPY secretion through membrane-associated estrogen receptor (ER)-\u03b1 in clonal, immortalized hypothalamic neurons","volume":"35","author":"Dhillon","year":"2011","journal-title":"Int J Obes (Lond)"},{"key":"2020052208494639500_CIT0028","doi-asserted-by":"crossref","first-page":"12735","DOI":"10.1073\/pnas.97.23.12735","article-title":"Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity","volume":"97","author":"Jones","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020052208494639500_CIT0029","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/j.1463-1326.2005.00545.x","article-title":"Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women","volume":"8","author":"Salpeter","year":"2006","journal-title":"Diabetes Obes Metab"},{"key":"2020052208494639500_CIT0030","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0167-0115(97)01007-0","article-title":"Endocrine function of neuropeptide Y knockout mice","volume":"70","author":"Erickson","year":"1997","journal-title":"Regul Pept"},{"key":"2020052208494639500_CIT0031","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1210\/en.2012-1340","article-title":"Minireview: translational animal models of human menopause: challenges and emerging opportunities","volume":"153","author":"Diaz Brinton","year":"2012","journal-title":"Endocrinology"},{"key":"2020052208494639500_CIT0032","article-title":"Ovariectomy and 17\u03b2-estradiol replacement in rats and mice: a visual demonstration","volume":"e 4013","author":"Str\u00f6m","year":"2012","journal-title":"J Vis Exp"},{"key":"2020052208494639500_CIT0033","first-page":"38","article-title":"Biological effects of hormone replacement therapy in relation to serum estradiol levels","volume":"56","author":"Yasui","year":"2001","journal-title":"Horm Res"},{"key":"2020052208494639500_CIT0034","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1177\/00912700222011166","article-title":"Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population","volume":"42","author":"Gavaler","year":"2002","journal-title":"J Clin Pharmacol"},{"key":"2020052208494639500_CIT0035","doi-asserted-by":"crossref","first-page":"12729","DOI":"10.1073\/pnas.97.23.12729","article-title":"Increased adipose tissue in male and female estrogen receptor-alpha knockout mice","volume":"97","author":"Heine","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020052208494639500_CIT0036","doi-asserted-by":"crossref","first-page":"e1000108","DOI":"10.1371\/journal.pgen.1000108","article-title":"Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a negative cross-talk with PPARgamma","volume":"4","author":"Foryst-Ludwig","year":"2008","journal-title":"PLoS Genet"},{"key":"2020052208494639500_CIT0037","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.genm.2011.05.010","article-title":"Increased estrogen receptor \u03b2 in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats","volume":"8","author":"Tomicek","year":"2011","journal-title":"Gend Med"}],"container-title":["The Journals of Gerontology: Series A"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/75\/6\/1042\/33283412\/gly282.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/75\/6\/1042\/33283412\/gly282.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T11:15:50Z","timestamp":1720869350000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/75\/6\/1042\/5250443"}},"subtitle":[],"editor":[{"given":"Rozalyn","family":"Anderson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,12,17]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,12,17]]},"published-print":{"date-parts":[[2020,5,22]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/gly282","relation":{},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,6]]},"published":{"date-parts":[[2018,12,17]]}}}