Document Detail


Dysregulation of hepatic fatty acid metabolism in chronic kidney disease.
MedLine Citation:
PMID:  23045433     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here.
METHODS: Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined.
RESULTS: Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue.
CONCLUSION: Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride.
Authors:
Kyubok Jin; Keith Norris; Nosratola D Vaziri
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-08
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  28     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-15     Completed Date:  2013-08-30     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  313-20     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
Diacylglycerol O-Acyltransferase / metabolism
Disease Models, Animal
Fatty Acids / metabolism*
Liver / metabolism*
Male
PPAR gamma / metabolism
Rats
Rats, Sprague-Dawley
Renal Insufficiency, Chronic / metabolism*,  physiopathology*
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
MD000182/MD/NIMHD NIH HHS; P20 MD000182/MD/NIMHD NIH HHS; RR026138/RR/NCRR NIH HHS; S21 MD000103/MD/NIMHD NIH HHS; U54 MD007598/MD/NIMHD NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/Fatty Acids; 0/PPAR gamma; 0/Triglycerides; 0/Wbscr14 protein, rat; EC 2.3.1.20/Dgat1 protein, rat; EC 2.3.1.20/Diacylglycerol O-Acyltransferase
Comments/Corrections

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