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CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL\/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1\u03b2, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1\u03b2, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1\u03b2, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36\/NLRP3\/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy. <\/jats:p>","DOI":"10.1152\/ajprenal.00536.2017","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T10:12:48Z","timestamp":1537351968000},"page":"F1720-F1731","source":"Crossref","is-referenced-by-count":45,"title":["Palmitate aggravates proteinuria-induced cell death and inflammation via CD36-inflammasome axis in the proximal tubular cells of obese mice"],"prefix":"10.1152","volume":"315","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-0083","authenticated-orcid":false,"given":"Lung-Chih","family":"Li","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan"},{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 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