Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

Yang P¹, Xiao Y¹, Luo X¹, Zhao Y², Zhao L¹, Wang Y¹, Wu T¹, Wei L¹, Chen Y³.

J Lipid Res. 2017 Jul;58(7):1417-1427. doi: 10.1194/jlr.M076216. Epub  2017 May 23

PMID:28536108                    DOI:10.1194/jlr.M076216

Abstract

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD.