{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:43:43Z","timestamp":1785473023057,"version":"3.56.0"},"posted":{"date-parts":[[2024,7,4]]},"group-title":"Neuroscience","reference-count":79,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>\n                    Kisspeptin, encoded by the\n                    <jats:italic>Kiss1<\/jats:italic>\n                    gene, ties puberty and fertility to energy status; however, the metabolic factors that control\n                    <jats:italic>Kiss1<\/jats:italic>\n                    -expressing cells need to be clarified.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    To evaluate the impact of IGF-1 on the metabolic and reproductive functions of kisspeptin producing cells, we created mice with IGF-1 receptor deletion driven by the\n                    <jats:italic>Kiss1<\/jats:italic>\n                    promoter (IGF1R\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice). Previous studies have shown IGF-1 and insulin can bind to each other\u2019s receptor, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we also generated mice with simultaneous deletion of the IGF1R and insulin receptor (IR) in\n                    <jats:italic>Kiss1<\/jats:italic>\n                    -expressing cells (IGF1R\/IR\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Loss of IGF1R in\n                    <jats:italic>Kiss1<\/jats:italic>\n                    cells caused stunted body length. In addition, female IGF1R\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice displayed lower body weight and food intake plus higher energy expenditure and physical activity. This phenotype was linked to higher proopiomelanocortin (POMC) expression and heightened brown adipose tissue (BAT) thermogenesis. Male IGF1R\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice had mild changes in metabolic functions. Moreover, IGF1R\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice of both sexes experienced delayed puberty. Notably, male IGF1R\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice had impaired adulthood fertility accompanied by lower gonadotropin and testosterone levels. Thus, IGF1R in\n                    <jats:italic>Kiss1<\/jats:italic>\n                    -expressing cells impacts metabolism and reproduction in a sex-specific manner. IGF1R\/IR\n                    <jats:sup>Kiss1<\/jats:sup>\n                    mice had higher fat mass and glucose intolerance, suggesting IGF1R and IR in\n                    <jats:italic>Kiss1<\/jats:italic>\n                    -expressing cells together regulate body composition and glucose homeostasis.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Overall, our study shows that IGF1R and IR in\n                    <jats:italic>Kiss1<\/jats:italic>\n                    have cooperative roles in body length, metabolism, and reproduction.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.02.601722","type":"posted-content","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T19:05:13Z","timestamp":1720119913000},"source":"Crossref","is-referenced-by-count":6,"title":["IGF-1 Acts through Kiss1-expressing Cells to Influence Metabolism and Reproduction"],"prefix":"10.64898","author":[{"given":"Mengjie","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seamus M.","family":"Pugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Daboul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-9215","authenticated-orcid":false,"given":"Jennifer W.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024070909401426000_2024.07.02.601722v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.70"},{"key":"2024070909401426000_2024.07.02.601722v1.2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00009.2010"},{"key":"2024070909401426000_2024.07.02.601722v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-019-0511-x"},{"key":"2024070909401426000_2024.07.02.601722v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3492"},{"key":"2024070909401426000_2024.07.02.601722v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000423107"},{"key":"2024070909401426000_2024.07.02.601722v1.6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.mce.2006.04.026","article-title":"Novel signals for the integration of energy balance and reproduction","volume":"254-255","year":"2006","journal-title":"Mol Cell Endocrinol"},{"key":"2024070909401426000_2024.07.02.601722v1.7","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1282"},{"key":"2024070909401426000_2024.07.02.601722v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.05.060"},{"issue":"8","key":"2024070909401426000_2024.07.02.601722v1.9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41574-020-0363-7","article-title":"Metabolic regulation of kisspeptin - the link between energy balance and reproduction","volume":"16","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"2024070909401426000_2024.07.02.601722v1.10","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-18-0108"},{"key":"2024070909401426000_2024.07.02.601722v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.01.022"},{"key":"2024070909401426000_2024.07.02.601722v1.12","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0500"},{"key":"2024070909401426000_2024.07.02.601722v1.13","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0096"},{"key":"2024070909401426000_2024.07.02.601722v1.14","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0337"},{"key":"2024070909401426000_2024.07.02.601722v1.15","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0005"},{"key":"2024070909401426000_2024.07.02.601722v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2009.01892.x"},{"key":"2024070909401426000_2024.07.02.601722v1.17","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00389"},{"key":"2024070909401426000_2024.07.02.601722v1.18","doi-asserted-by":"crossref","unstructured":"Conde, K. , Kulyk, D. , Vanschaik, A. , Daisey, S. , Rojas, C. , Wiersielis, K. , et al., 2022. 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