Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK

Proceedings of the National Academy of Sciences of the United States of America
Ying LuoJun-Yan Liu

Abstract

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 an...Continue Reading

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Citations

May 27, 2020·Journal of Cellular Physiology·Xiao-Qin LuoCha-Xiang Guan
Oct 11, 2020·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Jianan ZhangGuodong Zhang
Mar 30, 2021·Frontiers in Molecular Biosciences·Mouad HamzaouiDominique Guerrot
Jul 23, 2021·Physiological Reports·Andrea Sánchez-NavarroNorma A Bobadilla

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