{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:50:52Z","timestamp":1791528652363,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Cariplo Foundation","doi-asserted-by":"publisher","award":["2013-0786"],"award-info":[{"award-number":["2013-0786"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously demonstrated that Npy1rrfb mice, which carry the conditional inactivation of the Npy1r gene in forebrain principal neurons, display a sexually dimorphic phenotype, with male mice showing metabolic, hormonal and behavioral effects and females being only marginally affected. Moreover, exposure of Npy1rrfb male mice to a high-fat diet (HFD) increased body weight growth, adipose tissue, blood glucose levels and caloric intake compared to Npy1r2lox male controls. We used conditional knockout Npy1rrfb and Npy1r2lox control mice to examine whether forebrain disruption of the Npy1r gene affects susceptibility to obesity and associated disorders of cycling and ovariectomized (ovx) female mice in a standard diet (SD) regimen or exposed to an HFD for 3 months. The conditional deletion of the Npy1r gene increased body weight and subcutaneous white adipose tissue weight in both SD- and HFD-fed ovx females but not in cycling females. Moreover, compared with ovx control females on the same diet regimen, Npy1rrfb females displayed increased microglia number and activation, increased expression of Neuropeptide Y (NPY)-immunoreactivity (IR) and decreased expression of proopiomelanocortin-IR in the hypothalamic arcuate nucleus (ARC). These results suggest that in the ARC NPY-Y1R reduces the susceptibility to obesity of female mice with low levels of gonadal hormones and that this effect may be mediated via NPY-Y1R ability to protect the brain against neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms23116351","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T21:56:52Z","timestamp":1654552612000},"page":"6351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hypothalamic NPY-Y1R Interacts with Gonadal Hormones in Protecting Female Mice against Obesity and Neuroinflammation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7799-4769","authenticated-orcid":false,"given":"Alessandra","family":"Oberto","sequence":"first","affiliation":[{"name":"Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"},{"name":"Department of Neuroscience, University of Turin, C.so Massimo d\u2019Azeglio 52, 10126 Turin, Italy"},{"name":"Neuroscience Institute of Turin, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-716X","authenticated-orcid":false,"given":"Ilaria","family":"Bertocchi","sequence":"additional","affiliation":[{"name":"Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"},{"name":"Department of Neuroscience, University of Turin, C.so Massimo d\u2019Azeglio 52, 10126 Turin, Italy"},{"name":"Neuroscience Institute of Turin, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Longo","sequence":"additional","affiliation":[{"name":"Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8067-8561","authenticated-orcid":false,"given":"Sara","family":"Bonzano","sequence":"additional","affiliation":[{"name":"Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"},{"name":"Department of Life Sciences and Systems Biology (DBIOS), University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9580-5458","authenticated-orcid":false,"given":"Silvia","family":"Paterlini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, Behavioral Biology Lab\u2014Parco Area delle Scienze 11A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Meda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-5266","authenticated-orcid":false,"given":"Sara","family":"Della Torre","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy"},{"name":"Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-4260","authenticated-orcid":false,"given":"Paola","family":"Palanza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, Behavioral Biology Lab\u2014Parco Area delle Scienze 11A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Maggi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy"},{"name":"Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9638-7240","authenticated-orcid":false,"given":"Carola","family":"Eva","sequence":"additional","affiliation":[{"name":"Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"},{"name":"Department of Neuroscience, University of Turin, C.so Massimo d\u2019Azeglio 52, 10126 Turin, Italy"},{"name":"Neuroscience Institute of Turin, Regione Gonzole 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1097\/GME.0b013e31827fdd8c","article-title":"Aging, obesity, and multimorbidity in women 50 years or older: A population-based study","volume":"20","author":"Osis","year":"2013","journal-title":"Menopause"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E1695","DOI":"10.1210\/jc.2012-1614","article-title":"Do changes in sex steroid hormones precede or follow increases in body weight during the menopause transition? 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