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The CaSR is expressed in the brain, including in hypothalamic growth hormone stimulating GHRH and anorectic POMC neurons that control growth and energy homeostasis. We embryonically deleted the\n                  <jats:italic>Casr<\/jats:italic>\n                  gene in neurons to create\n                  <jats:sup>Neuron<\/jats:sup>\n                  CaSR\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice to delineate the role of this receptor in regulating growth, skeletal development, and energy metabolism.\n                  <jats:sup>Neuron<\/jats:sup>\n                  CaSR\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice had reduced size, weight and bone mass compared to littermate controls, with a dysregulated growth hormone axis. They also showed increased adiposity and circulating leptin levels, leptin resistance, and decreased glucose tolerance, along with reduced expression of the anorectic precursor peptide POMC and secondary increases in the expression of the anorectic peptide AgRP in the hypothalamus of\n                  <jats:sup>Neuron<\/jats:sup>\n                  CaSR\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice. Knockdown of CaSR in adult mice specifically in the hypothalamic arcuate nucleus, where GHRH, POMC and AgRP neurons reside, also resulted in increased body weight, adiposity, leptin resistance, and glucose intolerance, and reduced bone mass. Together these data suggest that neuronal CaSR critically regulates energy and skeletal metabolism and body growth by modulating hypothalamic function, representing a new paradigm for central integration of calcaemic activities with body function.\n                <\/jats:p>","DOI":"10.1101\/2025.05.22.655605","type":"posted-content","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T14:25:17Z","timestamp":1748355917000},"source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Ca\n                  <sup>2+<\/sup>\n                  -Sensing Receptor (CaSR) Regulates Hypothalamic Function to Control Energy and Skeletal Metabolism in Mice"],"prefix":"10.64898","author":[{"given":"Jennifer","family":"Park-Sigal","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Department of Veterans Affairs Medical Center, and the UCSF Diabetes Center3, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Norton","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ling","family":"Tu","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Department of Veterans Affairs Medical Center, and the UCSF Diabetes Center3, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Department of Veterans Affairs Medical Center, and the UCSF Diabetes Center3, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Fadahunsi","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Investigative 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