TY - JOUR T1 - Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia-Reperfusion–Induced Kidney and Liver Injury JF - Molecular Pharmacology JO - Mol Pharmacol SP - 239 LP - 250 DO - 10.1124/mol.117.111146 VL - 93 IS - 3 AU - You-Jin Choi AU - Dong Zhou AU - Anne Caroline S. Barbosa AU - Yongdong Niu AU - Xiudong Guan AU - Meishu Xu AU - Songrong Ren AU - Thomas D. Nolin AU - Youhua Liu AU - Wen Xie Y1 - 2018/03/01 UR - http://molpharm.aspetjournals.org/content/93/3/239.abstract N2 - Acute kidney injury (AKI) is associate with high mortality. Despite evidence of AKI-induced distant organ injury, a relationship between AKI and liver injury has not been clearly established. The goal of this study is to investigate whether renal ischemia-reperfusion (IR) can affect liver pathophysiology. We showed that renal IR in mice induced fatty liver and compromised liver function through the downregulation of constitutive androstane receptor (CAR; −90.4%) and inhibition of hepatic very-low-density lipoprotein triglyceride (VLDL-TG) secretion (−28.4%). Treatment of mice with the CAR agonist 1,4-bis[2-(3,5 dichloropyridyloxy)] benzene (TCPOBOP) prevented the development of AKI-induced fatty liver and liver injury, which was associated with the attenuation of AKI-induced inhibition of VLDL-TG secretion. The hepatoprotective effect of TCPOBOP was abolished in CAR−/− mice. Interestingly, alleviation of fatty liver by TCPOBOP also improved the kidney function, whereas CAR ablation sensitized mice to AKI-induced kidney injury and lethality. The serum concentrations of interleukin-6 (IL-6) were elevated by 27-fold after renal IR, but were normalized in TCPOBOP-treated AKI mice, suggesting that the increased release of IL-6 from the kidney may have mediated the AKI responsive liver injury. Taken together, our results revealed an interesting kidney-liver organ cross-talk in response to AKI. Given the importance of CAR in the pathogenesis of renal IR–induced fatty liver and impaired kidney function, fatty liver can be considered as an important risk factor for kidney injury, and a timely management of hepatic steatosis by CAR activation may help to restore kidney function in patients with AKI or kidney transplant. ER -