{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:23:34Z","timestamp":1789791814904,"version":"4.0.1"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"22","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,11,30]]},"abstract":"<jats:p>Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (classes II\u2013III) and db\/db mice compared with the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry (IHC) staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol regulatory element binding protein-1 (SREBP-1) was clearly up-regulated, which was positively correlated with the tubulointerstitial damage score and inflammation. Furthermore, the urine ADRP content significantly increased in DKD patients compared with the control, which positively correlated with abnormal lipid metabolism, serum creatinine, urine N-acetyl-\u03b2-glucosaminidase (NAG), albumin excretion (albumin-to-creatinine ratio (ACR)), and tumor necrosis factor-\u03b1 (TNF-\u03b1) expression. However, there was no significant difference observed in plasma ADRP levels. In addition, the expression of SREBP-1 protein was dramatically increased in peripheral blood mononuclear cells (PBMCs) isolated from DKD patients, which was also tightly correlated with urine NAG, ACR, and TNF-\u03b1 levels. In vitro studies demonstrated increased ADRP and SREBP-1 expression accompanied by lipid accumulation in HK-2 cells cultured in high glucose (HG). HG induced high levels of TNF-\u03b1 expression, which was partially blocked by transfection of ADRP siRNA or SREBP-1 siRNA. These data indicated that ADRP and SREBP-1 are crucial factors that mediate lipid accumulation with tubular damage and inflammation in DKD, and ectopic lipid accumulation may serve as a novel therapeutic target for amelioration of tubular injury in DKD.<\/jats:p>","DOI":"10.1042\/cs20180702","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T20:25:44Z","timestamp":1540239944000},"page":"2407-2422","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease"],"prefix":"10.1042","volume":"132","author":[{"given":"Wenxia","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5488-5583","authenticated-orcid":false,"given":"Li","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,11,22]]},"reference":[{"key":"2021113011005509300_B1","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1056\/NEJMc1602469","article-title":"Trends in chronic kidney disease in China","volume":"375","author":"Zhang","year":"2016","journal-title":"N. 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