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In the chronic phase of this inflammatory response, bone marrow\u2010derived and lymphoid cells are chemoattracted to this region, partially mitigating high\u2010fat diet (HFD)\u2010induced metabolic impairments. In rodents, the onset and magnitude of this inflammation differ between males and females, reflecting sex\u2010specific patterns of metabolic regulation. However, how the hypothalamic chemokine profile evolves during HFD\u2010induced inflammation, and whether it is influenced by biological sex, remains unclear. Here, male and female C57BL\/6J mice were fed a HFD for 1, 3, 14, or 28\u2009days. To isolate the role of ovarian hormones in modulating hypothalamic chemokine profile, we also analyzed ovariectomized (OVX) females with or without estrogen replacement. Quantitative polymerase chain reaction\u2010based expression analysis revealed that most chemokines and their receptors were transiently modulated in the hypothalamus during the course of the HFD exposure, showing reduced levels in the acute phase and normalization during the chronic phase. Despite the modest sex\u2010dependent effects observed, messenger RNA expression of the chemokine receptor C\u2013X\u2013C motif chemokine receptor 3 (CXCR3) was significantly higher in females than in males after 14 and 28\u2009days of HFD, suggesting faster recruitment of CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    immune cells that may contribute to female protection against metabolic dysfunction. Females lacking ovarian hormone production displayed increased hypothalamic expression of\n                    <jats:italic>Cxcr3<\/jats:italic>\n                    and\n                    <jats:italic>Ccl2<\/jats:italic>\n                    . Only\n                    <jats:italic>Cxcr3<\/jats:italic>\n                    expression was partially normalized by estradiol treatment, suggesting that non\u2010estrogenic ovarian factors may play a role in modulating specific chemokine signaling pathways. Together, our findings show that hypothalamic chemokine signaling is dynamically and transiently regulated throughout the phases of HFD\u2010induced inflammation, with\n                    <jats:italic>Cxcr3<\/jats:italic>\n                    modulation by HFD and ovarian hormones contributing to sex\u2010specific resilience against metabolic inflammation.\n                  <\/jats:p>","DOI":"10.1111\/jne.70215","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:15:13Z","timestamp":1782389713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ovarian hormones and high\u2010fat diet duration distinctively modulate hypothalamic chemokine profile"],"prefix":"10.1111","volume":"38","author":[{"given":"Alexia Guimaraes Batista","family":"Augusto","sequence":"first","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Ariozi","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Vinicius Sousa","family":"Cavalheiro","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"},{"name":"School of Medical Sciences, Department of Translational Medicine\u2014Section of Pharmacology University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Stefanini","family":"Mantovan","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"},{"name":"School of Medical Sciences, Department of Translational Medicine\u2014Section of Pharmacology University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Silva","family":"Bergantini","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"},{"name":"School of Medical Sciences, Department of Pathophysiology University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolly Porto","family":"Marin","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"},{"name":"School of Medical Sciences, Department of Translational Medicine\u2014Section of Pharmacology University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"dos Santos Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"},{"name":"School of Medical Sciences, Department of Pathophysiology University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licio Augusto","family":"Velloso","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center University of Campinas  Campinas Brazil"},{"name":"School of Medical Sciences, Department of Pathophysiology University of Campinas  Campinas Brazil"},{"name":"National Institute of Science and Technology on Neuroimmunomodulation  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9032-1411","authenticated-orcid":false,"given":"Natalia Ferreira","family":"Mendes","sequence":"additional","affiliation":[{"name":"Laboratory of Cell 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35007534"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010021\u201000408\u20105"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004\u20101520"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59660"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154\u2010025\u201009992\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.108983"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.11.018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101595\u20104"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.070"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.033"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010022\u201002519\u20106"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004\u20100726"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201063260\u20105_4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104344"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.05.015"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201057918\u2010z"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.95044"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01992"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154\u2010025\u201009983\u20104"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293\u2010025\u201000699\u20103"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2020.107795"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366\u2010022\u201001174\u20104"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00098.2025"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23882"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293\u2010024\u201000608\u20100"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1276"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154846"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008\u20101405"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2012.71"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2022.151886"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801806"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20100390"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122850"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010025\u201003522\u20103"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010018\u20102596\u20106"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14556"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2010.01.003"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.07.161"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000490"}],"container-title":["Journal 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