{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:30:20Z","timestamp":1790775020477,"version":"4.1.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,10,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    LEOPARD syndrome (multiple\n                    <jats:underline>L<\/jats:underline>\n                    entigines,\n                    <jats:underline>E<\/jats:underline>\n                    lectrocardiographic conduction abnormalities,\n                    <jats:underline>O<\/jats:underline>\n                    cular hypertelorism,\n                    <jats:underline>P<\/jats:underline>\n                    ulmonary stenosis,\n                    <jats:underline>A<\/jats:underline>\n                    bnormal genitalia,\n                    <jats:underline>R<\/jats:underline>\n                    etardation of growth, sensorineural\n                    <jats:underline>D<\/jats:underline>\n                    eafness; LS) is a rare genetic disease associating various developmental defects mainly caused by inactivating mutations of the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). SHP2 is a key regulator of essential signaling pathways (MAPK, PI3K), which confer on SHP2 major roles in development and metabolism control. However, nothing is known about the metabolic status of LS. We thus performed an extensive metabolic exploration of an original LS mouse model. These mice display a lean phenotype (reduced adiposity, improved carbohydrate metabolism), translating into resistance to obesity and associated disorders upon obesogenic diet. This phenotype correlated with defective adipogenesis, better insulin signaling, and enhanced energy expenditure and was partially corrected by MAPK inhibition. Preliminary data in LS patients are in agreement with these findings.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1406107111","type":"journal-article","created":{"date-parts":[[2014,10,6]],"date-time":"2014-10-06T22:54:30Z","timestamp":1412636070000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity"],"prefix":"10.1073","volume":"111","author":[{"given":"Myl\u00e8ne","family":"Tajan","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1048, F-31432 Toulouse, France;"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, Universit\u00e9 de Toulouse, Universit\u00e9 Paul Sabatier, F-31432 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Batut","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1048, F-31432 Toulouse, France;"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, Universit\u00e9 de Toulouse, Universit\u00e9 Paul Sabatier, F-31432 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cadoudal","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1048, F-31432 Toulouse, France;"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, Universit\u00e9 de Toulouse, Universit\u00e9 Paul Sabatier, F-31432 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Deleruyelle","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1048, F-31432 Toulouse, France;"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, Universit\u00e9 de Toulouse, Universit\u00e9 Paul Sabatier, F-31432 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Le Gonidec","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1048, F-31432 Toulouse, France;"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, Universit\u00e9 de Toulouse, Universit\u00e9 Paul Sabatier, F-31432 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Saint Laurent","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1048, F-31432 Toulouse, France;"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, Universit\u00e9 de Toulouse, Universit\u00e9 Paul 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