Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats

作者：Muroya Yoshikazu; Ito Osamu^*; Rong Rong; Takashima Kenta; Ito Daisuke; Cao Pengyu; Nakamura Yasuhiro; Joh Kensuke; Kohzuki Masahiro

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2012, 303(7): F1070-F1079.

DOI：10.1152/ajprenal.00365.2011

• albuminuria
• lipid accumulation
• lipotoxicity
• fatty acid metabolism
• proximal tubular epithelial cells
• puromycin aminonucleoside

Muroya Y, Ito O, Rong R, Takashima K, Ito D, Cao P, Nakamura Y, Joh K, Kohzuki M. Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats. Am J Physiol Renal Physiol 303: F1070-F1079, 2012. First published August 8, 2012; doi:10.1152/ajprenal.00365.2011.-Proteinuria is considered to play an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. Fatty acid-binding albumins are filtered through glomeruli and reabsorbed into proximal tubular epithelial cells (PTECs). However, the role of fatty acid metabolism associated with albuminuria in the development of tubulointerstitial damage remains unclear. Thus, the present study was designed to determine the changes of fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome, Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited hypoalbuminemia were treated with a single injection of puromycin aminonucleoside (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1 alpha and estrogen-related receptor (ERR)alpha also significantly decreased, without changes in the expression of PPAR-alpha. In NARs, PAN treatment induced proteinuria but not albuminuria and did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of MCAD, PGC-1 alpha, or ERR alpha did not change in the kidney cortex of PAN-treated NARs, but the expression of CYP4A significantly decreased. These results indicate that massive albuminuria causes tubular damage and lipid accumulation with the reduction of MCAD, CYP4A, PGC-1 alpha, and ERR alpha in PTECs.

• 出版日期2012-10