RGD Reference Report - Expression profiling of hepatic genes associated with lipid metabolism in nephrotic rats. - Rat Genome Database

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Expression profiling of hepatic genes associated with lipid metabolism in nephrotic rats.

Authors: Zhou, Y  Zhang, X  Chen, L  Wu, J  Dang, H  Wei, M  Fan, Y  Zhang, Y  Zhu, Y  Wang, N  Breyer, MD  Guan, Y 
Citation: Zhou Y, etal., Am J Physiol Renal Physiol. 2008 Sep;295(3):F662-71. Epub 2008 Jul 9.
RGD ID: 2313652
Pubmed: PMID:18614621   (View Abstract at PubMed)
PMCID: PMC2536868   (View Article at PubMed Central)
DOI: DOI:10.1152/ajprenal.00046.2008   (Journal Full-text)

Hyperlipidemia is one of the major features of nephrotic syndrome (NS). Although many factors have been implicated in the pathogenesis of NS-related dyslipidemia, the underlying mechanisms remain largely uncharacterized. The present study was designed to examine the gene profile associated with lipid metabolism in the livers of nephrotic rats. NS was created in male Sprague-Dawley rats (n = 6) receiving sequential intraperitoneal injections of puromycin aminonucleoside. Analysis by Affymetrix assay, quantitative RT-PCR, and Northern and Western blotting revealed 21 genes associated with cholesterol and fatty acid metabolism. Eight genes involved in cholesterol metabolism, Apo A-I, Acly, Acat, Mpd, Fdps, Ss, Lss, and Nsdhl, were significantly upregulated under NS. Four genes involved in fatty acid biosynthesis, Acc, FAS, ELOVL 2, and ELOVL6, and three critical for triglyceride biosynthesis, Gpam, Agpat 3, and Dgat 1, were significantly upregulated, whereas two genes involved in fatty acid oxidation, Dci and MCAD, were downregulated. Expression of several genes in sterol-regulatory element-binding protein (SREBP)-1 activation was also aberrantly altered in nephrotic livers. The expression and transcriptional activity of SREBP-1 but not SREBP-2 were increased in nephrotic rats as assessed by real-time PCR, immunoblotting, and gel shift assays. The upregulation of hepatic genes involved in cholesterol biosynthesis may play an important role in the pathogenesis of hypercholesterolemia, whereas upregulation of genes participating in hepatic fatty acid and triglyceride biosynthesis and downregulation of genes involved in hepatic fatty acid oxidation may contribute to hypertriglyceridemia in nephrotic rats. Activation of SREBP-1 transcription factor may represent an underlying molecular mechanism of hyperlipidemia in NS.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Apoa1  (apolipoprotein A1)
Gpam  (glycerol-3-phosphate acyltransferase, mitochondrial)

Genes (Mus musculus)
Apoa1  (apolipoprotein A-I)
Gpam  (glycerol-3-phosphate acyltransferase, mitochondrial)

Genes (Homo sapiens)
APOA1  (apolipoprotein A1)
GPAM  (glycerol-3-phosphate acyltransferase, mitochondrial)


Additional Information