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However, the molecular mechanisms that enable hypothalamic neurons to detect primary nutrients remain elusive. Here, we identified l-type amino acid transporter 1 (LAT1) in hypothalamic leptin receptor\u2013expressing (LepR-expressing) neurons as being important for systemic energy and bone homeostasis. We observed LAT1-dependent amino acid uptake in the hypothalamus, which was compromised in a mouse model of obesity and diabetes. Mice lacking LAT1 (encoded by solute carrier transporter 7a5,\n                    <jats:italic>Slc7a5<\/jats:italic>\n                    ) in LepR-expressing neurons exhibited obesity-related phenotypes and higher bone mass.\n                    <jats:italic>Slc7a5<\/jats:italic>\n                    deficiency caused sympathetic dysfunction and leptin insensitivity in LepR-expressing neurons before obesity onset. Importantly, restoring\n                    <jats:italic>Slc7a5<\/jats:italic>\n                    expression selectively in LepR-expressing ventromedial hypothalamus neurons rescued energy and bone homeostasis in mice deficient for\n                    <jats:italic>Slc7a5<\/jats:italic>\n                    in LepR-expressing cells. Mechanistic target of rapamycin complex-1 (mTORC1) was found to be a crucial mediator of LAT1-dependent regulation of energy and bone homeostasis. These results suggest that the LAT1\/mTORC1 axis in LepR-expressing neurons controls energy and bone homeostasis by fine-tuning sympathetic outflow, thus providing in vivo evidence of the implications of amino acid sensing by hypothalamic neurons in body homeostasis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.154925","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T12:00:41Z","timestamp":1677758441000},"source":"Crossref","is-referenced-by-count":12,"title":["l-Type amino acid transporter 1 in hypothalamic neurons in mice maintains energy and bone homeostasis"],"prefix":"10.1172","volume":"8","author":[{"given":"Gyujin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Bioactive Molecules, Laboratory Pharmacology, Gifu Pharmaceutical University, Gifu, Japan."},{"name":"Department of Neurobiology, Northwestern University, Evanston, Illinois, 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