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Browning of white adipose tissue (WAT) is one of the significant factors that contribute to energy wasting in cachexia. By utilizing a cell implantation model, we demonstrate here that the lipid mobilizing factor zinc\u2010\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    \u2010glycoprotein (ZAG) induces WAT browning in mice. Increased circulating levels of ZAG not only induced lipolysis in adipose tissues but also caused robust browning in WAT. Stimulating WAT progenitors with ZAG recombinant protein or expression of ZAG in mouse embryonic fibroblasts (MEFs) strongly enhanced brown\u2010like differentiation. At the molecular level, ZAG stimulated peroxisome proliferator\u2013activated receptor \u03b3 (PPAR\u03b3) and early B cell factor 2 expression and promoted their recruitment to the PR\/SET domain 16 (Prdm16) promoter, leading to enhanced expression of Prdm16, which determines brown cell fate. In brown adipose tissue, ZAG stimulated the expression of PPAR\u03b3 and PPAR\u03b3 coactivator 1\u03b1 and promoted recruitment of PPAR\u03b3 to the uncoupling protein 1 (Ucp1) promoter, leading to increased expression of Ucp1. Overall, our results reveal a novel function of ZAG in WAT browning and highlight the targeting of ZAG as a potential therapeutic application in humans with cachexia.\u2014Elattar, S., Dimri, M., Satyanarayana, A. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting. FASEB J. 32, 4727\u20134743 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701465rr","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T16:02:08Z","timestamp":1521820928000},"page":"4727-4743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting"],"prefix":"10.1096","volume":"32","author":[{"given":"Sawsan","family":"Elattar","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Georgia Cancer Center Augusta University Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manali","family":"Dimri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Georgia Cancer Center Augusta University Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ande","family":"Satyanarayana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Georgia Cancer Center Augusta University Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/83.4.735"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc927"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.011"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2223"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.10.971"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115767"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.06.011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3829"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3324"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07182"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.06.001"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.01.015"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08262"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44271"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.11.001"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3361"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S0021-9258(18)64243-7","article-title":"Preparation and properties of Zn-\u03b12-glycoprotein of normal human plasma","volume":"236","author":"Burgi W.","year":"1961","journal-title":"J. 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