{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:44:11Z","timestamp":1790711051782,"version":"4.1.0"},"reference-count":71,"publisher":"American Society for Clinical Investigation","issue":"23","funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["HD069702"],"award-info":[{"award-number":["HD069702"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,7]]},"abstract":"<jats:p>\n                    The role of PI3K in leptin physiology has been difficult to determine due to its actions downstream of several metabolic cues, including insulin. Here, we used a series of mouse models to dissociate the roles of specific PI3K catalytic subunits and of insulin receptor (InsR) downstream of leptin signaling. We show that disruption of p110\u03b1 and p110\u03b2 subunits in leptin receptor cells (LR\n                    <jats:sup>\u0394\u03b1+\u03b2<\/jats:sup>\n                    ) produces a lean phenotype associated with increased energy expenditure, locomotor activity, and thermogenesis. LR\n                    <jats:sup>\u0394\u03b1+\u03b2<\/jats:sup>\n                    mice have deficient growth and delayed puberty. Single subunit deletion (i.e., p110\u03b1 in LR\n                    <jats:sup>\u0394\u03b1<\/jats:sup>\n                    ) resulted in similarly increased energy expenditure, deficient growth, and pubertal development, but LR\n                    <jats:sup>\u0394\u03b1<\/jats:sup>\n                    mice have normal locomotor activity and thermogenesis. Blunted PI3K in leptin receptor (LR) cells enhanced leptin sensitivity in metabolic regulation due to increased basal hypothalamic pAKT, leptin-induced pSTAT3, and decreased PTEN levels. However, these mice are unresponsive to leptin\u2019s effects on growth and puberty. We further assessed if these phenotypes were associated with disruption of insulin signaling. LR\n                    <jats:sup>\u0394InsR<\/jats:sup>\n                    mice have no metabolic or growth deficit and show only mild delay in pubertal completion. Our findings demonstrate that PI3K in LR cells plays an essential role in energy expenditure, growth, and reproduction. These actions are independent from insulin signaling.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.96728","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T11:00:32Z","timestamp":1512558032000},"source":"Crossref","is-referenced-by-count":38,"title":["PI3K\u03b1 inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction"],"prefix":"10.1172","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-8785","authenticated-orcid":true,"given":"David","family":"Garcia-Galiano","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz C.","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Department of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Jose","family":"Donato","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Bellefontaine","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Toledo, Toledo, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean J.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer W.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Toledo, Toledo, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol F.","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2017,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04694"},{"issue":"7205","key":"B2","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature07091","article-title":"Essential roles of PI(3)K-p110\u03b2 in cell growth, metabolism and tumorigenesis","volume":"454","author":"Jia","year":"2008","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113966"},{"issue":"6858","key":"B4","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/35101657","article-title":"Intracellular signalling. 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