| AJTR Copyright © 2009-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2013;5(2):246-253
Original Article
Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome
Seungyeup Han, Nosratola D Vaziri, Pavan Gollapudi, Vincent Kwok, Hamid Moradi
Division of Nephrology and Hypertension, University of California, Irvine, USA; Department of Internal Medicine,
Keimyung University, School of medicine, Daegu, South Korea
Received December 24, 2012; Accepted February 8, 2013; Epub March 28, 2013; Published April 8, 2013
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 (AJTR1212003).
Keywords: Atherosclerosis, dyslipidemia, proteinuria, cardiovascular disease, fatty acids
Address correspondence to: Hamid Moradi, University of California, Irvine, Division of Nephrology and
Hypertension, 333 The City Blvd. Suite 400, Orange, CA 92868. Tel: 714-456-5142; Fax: 714-456-6034; E-mail:
hmoradi@uci.edu
Original Article
Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome
Seungyeup Han, Nosratola D Vaziri, Pavan Gollapudi, Vincent Kwok, Hamid Moradi
Division of Nephrology and Hypertension, University of California, Irvine, USA; Department of Internal Medicine,
Keimyung University, School of medicine, Daegu, South Korea
Received December 24, 2012; Accepted February 8, 2013; Epub March 28, 2013; Published April 8, 2013
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 (AJTR1212003).
Keywords: Atherosclerosis, dyslipidemia, proteinuria, cardiovascular disease, fatty acids
Address correspondence to: Hamid Moradi, University of California, Irvine, Division of Nephrology and
Hypertension, 333 The City Blvd. Suite 400, Orange, CA 92868. Tel: 714-456-5142; Fax: 714-456-6034; E-mail:
hmoradi@uci.edu
 | |  | |  | |  | |  | |  | |  |