{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:49:06Z","timestamp":1791283746448,"version":"4.1.0"},"reference-count":30,"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":[[2002,1,8]]},"abstract":"<jats:p>\n                    Targeting of the nuclear prostaglandin receptor peroxisome\n proliferator-activated receptor \u03b4 (PPAR\n                    <jats:italic>\u03b4<\/jats:italic>\n                    ) by\n homologous recombination results in placental defects and frequent\n (&gt;90%) midgestation lethality. Surviving\n                    <jats:italic>PPAR\u03b4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibit a striking\n reduction in adiposity relative to wild-type levels. This effect is not\n reproduced in mice harboring an adipose tissue-specific deletion of\n PPAR\n                    <jats:italic>\u03b4<\/jats:italic>\n                    , and thus likely reflects peripheral PPAR\u03b4\n functions in systemic lipid metabolism. Finally, we observe that\n PPAR\n                    <jats:italic>\u03b4<\/jats:italic>\n                    is dispensable for polyp formation in the\n intestine and colon of\n                    <jats:italic>APC<\/jats:italic>\n                    <jats:sup>min<\/jats:sup>\n                    mice,\n inconsistent with its recently proposed role in the establishment of\n colorectal tumors. Together, these observations reveal specific roles\n for PPAR\n                    <jats:italic>\u03b4<\/jats:italic>\n                    in embryo development and adipocyte\n physiology, but not cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.012610299","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"303-308","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":496,"title":["Effects of peroxisome proliferator-activated receptor \u03b4 on placentation, adiposity, and colorectal cancer"],"prefix":"10.1073","volume":"99","author":[{"given":"Yaacov","family":"Barak","sequence":"first","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Liao","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"He","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelita S.","family":"Ong","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerrold M.","family":"Olefsky","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Boland","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Howard Hughes Medical\r Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla,\r CA 92037; Department of Medicine, University of\r California, La Jolla, CA 92093; Division of Endocrinology\r and Metabolism, San Diego Veterans Affairs Medical Center, La\r Jolla, CA 92093; The Whittier Diabetes Institute, La\r Jolla, CA 92093; Department of Medicine and Cancer Center, University\r of California at San Diego School of Medicine, La Jolla, CA 92093;\r and Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90199-X"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.15.7355"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/rp.56.1.239"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199904000-00009"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90006-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80209-9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81575-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00164-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.22.12953"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90193-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091021198"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21920"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.8.974"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.12.1561"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4312"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81664-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1998.0593"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14602"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/5007"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.15.1739"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.7b.1318"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051630998"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1350108"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1787"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.14.5119-5128.2000"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7985020"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.3.563"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.19.5060"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3550481"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01554-4"}],"container-title":["Proceedings 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