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Hypogonadotropic hypogonadism is characterized by chronically insufficient gonadotropin hormone production, leading to reproductive and metabolic impairments, such as infertility and obesity. Polycystic ovary syndrome (PCOS) is characterized by accelerated gonadotropin hormone production leading to reproductive and metabolic deficits, including oligomenorrhea, infertility, and an increased risk of type 2 diabetes mellitus. Hypothalamic kisspeptin is a key regulator of gonadotropin secretion, and disruptions in kisspeptin signaling result in abnormal gonadotropin pulsatility. Emerging evidence also implicates kisspeptin in energy metabolism. This study investigates the neuroendocrine mechanisms by which kisspeptin within KNDy neurons influences metabolic homeostasis. Using a Pdyn\u2010Cre\/\n                    <jats:italic>Kiss1<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    knock\u2010out (\n                    <jats:italic>Kiss1<\/jats:italic>\n                    <jats:sup>Pdyn<\/jats:sup>\n                    KO) mouse model, we combined diet\u2010induced obesity, metabolic testing, and ovarian hormone depletion to assess the role of KNDy neuron kisspeptin in metabolic regulation and the interaction with sex steroids. Peripheral metabolism was more severely impacted in\n                    <jats:italic>Kiss1<\/jats:italic>\n                    <jats:sup>Pdyn<\/jats:sup>\n                    KO females than in KO males, with greater reproductive deficits observed in females. Abnormal glucose metabolism was partly attributable to the lack of ovarian steroids. Our findings indicate that loss of KNDy neuron kisspeptin in females promotes obesity through reduced energy expenditure without altering feeding behavior. Furthermore, this study identifies a female\u2010biased role for KNDy kisspeptin as a central integrator of reproductive and metabolic signals.\n                  <\/jats:p>","DOI":"10.1111\/jne.70208","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:31:36Z","timestamp":1780288296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>KNDy<\/scp>\n                    kisspeptin is required for metabolic homeostasis in female mice in an ovarian hormone\u2010independent manner"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-371X","authenticated-orcid":false,"given":"Nimisha","family":"Nandankar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Child Health Institute of New Jersey, Rutgers\u2010Robert Wood Johnson Medical School, Rutgers The State University of New Jersey  New Brunswick New Jersey 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