{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:14:07Z","timestamp":1791227647685,"version":"4.1.0"},"reference-count":69,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,1,2]]},"abstract":"<jats:p>\n                    The molecular mechanism underlying adipogenesis and the physiological functions of adipose tissue are not fully understood. We describe here a unique mouse model of severe lipodystrophy. Ablation of\n                    <jats:italic>Ptpn11\/Shp2<\/jats:italic>\n                    in adipocytes, mediated by\n                    <jats:italic>aP2-Cre<\/jats:italic>\n                    , led to premature death, lack of white fat, low blood pressure, compensatory erythrocytosis, and hepatic steatosis in\n                    <jats:italic>Shp2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>fat\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Fat transplantation partially rescued the lifespan and blood pressure in\n                    <jats:italic>Shp2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>fat\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, and administration of leptin also restored partially the blood pressure of mutant animals with endogenous leptin deficiency. Consistently, homozygous deletion of Shp2 inhibited adipocyte differentiation from embryonic stem (ES) cells. Biochemical analyses suggest a Shp2-TAO2-p38-p300-PPAR\u03b3 pathway in adipogenesis, in which Shp2 suppresses p38 activation, leading to stabilization of p300 and enhanced PPAR\u03b3 expression. Inhibition of p38 restored adipocyte differentiation from\n                    <jats:italic>Shp2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ES cells, and p38 signaling is also suppressed in obese patients and obese animals. These results illustrate an essential role of adipose tissue in mammalian survival and physiology and also suggest a common signaling mechanism involved in adipogenesis and obesity development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1213000110","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T21:28:16Z","timestamp":1355261296000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Nonreceptor tyrosine phosphatase Shp2 promotes adipogenesis through inhibition of p38 MAP kinase"],"prefix":"10.1073","volume":"110","author":[{"given":"Zhao","family":"He","sequence":"first","affiliation":[{"name":"Department of Pathology and Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0864;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0864;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Bauler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109-5620; 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