title: Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome.
abstract: Heavy proteinuria (nephrotic syndrome) is associated with hypercholesterolemia, hypertriglyceridemia and a high risk of atherosclerosis. Hypertriglyceridemia in nephrotic syndrome (NS) is partly due to increased TG and TG-rich lipoprotein production. However, data on the effect of NS on fatty acid production and catabolic machinery are limited. NS was induced in male Sprague Dawley rats by IP injection of puromycin aminonucleoside. Six weeks after the second injection the animals were euthanized, liver was harvested and processed. The NS group exhibited heavy proteinuria, hypercholesterolemia, hypertriglyceridemia, activation of SREBP-1 and LXR α/β, up-regulation of FAS, ACC and HMG CoA reductase. In contrast hepatic tissue ChREBP activity was reduced in NS excluding its role in upregulation of FA synthetic pathway. Despite increased expression and nuclear translocation of PPARα, expression of ACO and abundance of CPT and L-FABP, were decreased in the liver of nephrotic animals. Therefore, NS results in upregulation of FA production machinery. Increased hepatic fatty acid production capacity in NS is compounded by reduced FA catabolism, events that contribute to the associated hypertiglyceridemia.
authors.affiliation: Division of Nephrology and Hypertension, University of California Irvine, USA ; Department of Internal Medicine, Keimyung University, School of medicine Daegu, South Korea.
authors.forename: Seungyeup
authors.initials: S
authors.lastname: Han
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Pavan
authors.initials: P
authors.lastname: Gollapudi
authors.forename: Vincent
authors.initials: V
authors.lastname: Kwok
authors.forename: Hamid
authors.initials: H
authors.lastname: Moradi
keywords: Atherosclerosis; cardiovascular disease; dyslipidemia; fatty acids; proteinuria