{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:28:16Z","timestamp":1791044896559,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA180087"],"award-info":[{"award-number":["CA180087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Obesity is a leading cause of chronic kidney disease (CKD), but how obesity promotes renal injury remains poorly understood. Here we showed that ATP\u2010citrate lyase (ACL), an enzyme converting citrate to acetyl\u2010CoA, is highly induced in the kidney of overweight or obese patients with CKD and ob\/ob BTBR mice. ACL induction is associated with increased ectopic lipid accumulation (ELA), glomerulosclerosis, and albuminuria. Acety1\u2010CoA is the substrate for\n                    <jats:italic>de novo<\/jats:italic>\n                    lipogenesis as well as for histone acetylation. By raising acetyl\u2010CoA concentration ACL promotes H3K9\/14 and H3K27 hyperacetylation leading to up\u2010regulation of several rate\u2010limiting lipogenic enzymes and fibrogenic factors. On the other hand, the excess acetyl\u2010CoA generated as a result of ACL induction provides the substrate for these lipogenic enzymes to drive\n                    <jats:italic>de novo<\/jats:italic>\n                    lipogenesis leading to ELA, a detrimental event toward renal injury. In mesangial cells, ACL is synergistically induced by high glucose, palmitate, and TNF\u2010\u03b1\n                    <jats:italic>via<\/jats:italic>\n                    NF\u2010\u03baB and PKA pathways. Under these conditions, H3K9\/14 and H3K27 hyperacetylation, as well as the induction of the lipogenic and fibrogenic proteins, are completely blocked in the presence of an ACL inhibitor. Collectively, these data suggest that ACL is an epigenetic regulator that promotes renal ELA and fibrogenesis leading to renal injury in obesity.\u2014Chen, Y., Deb, D. K., Fu, X., Yi, B., Liang, Y., Du, J., He, L., Li, Y. C. ATP\u2010citrate lyase is an epigenetic regulator to promote obesity\u2010related kidney injury. FASEB J. 33, 9602\u20139615 (2019).\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.201900213r","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T13:56:51Z","timestamp":1559311011000},"page":"9602-9615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["ATP\u2010citrate lyase is an epigenetic regulator to promote obesity\u2010related kidney injury"],"prefix":"10.1096","volume":"33","author":[{"given":"Yinyin","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"},{"name":"Department of Nephrology Laboratory of Kidney Disease Hunan Provincial People's Hospital Hunan Normal University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip K.","family":"Deb","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"},{"name":"Department of Nephrology The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yi","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"},{"name":"Department of Nephrology The Third Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Laboratory of Kidney Disease Hunan Provincial People's Hospital Hunan Normal University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Du","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"He","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Chun","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences Department of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,31]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Centers for Disease Control and Prevention. 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