| Dysregulation of hepatic fatty acid metabolism in chronic kidney disease. | |
| | |
MedLine Citation:
|
PMID: 23045433 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
BackgroundChronic 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.MethodsMale 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.ResultsCompared 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.ConclusionLiver 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 |
Related Documents
:
|
23155453 - Reduced neonatal mortality in meishan piglets: a role for hepatic fatty acids? 18963323 - Ionic strength dependence of formation constants-i protonation constants of organic and... 16141533 - Cytochrome p450 4a isoform inhibitory profile of n-hydroxy-n'-(4-butyl-2-methylphenyl)-... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-10-8 |
Journal Detail:
|
Title: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Volume: - ISSN: 1460-2385 ISO Abbreviation: Nephrol. Dial. Transplant. Publication Date: 2012 Oct |
Date Detail:
|
Created Date: 2012-10-9 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8706402 Medline TA: Nephrol Dial Transplant Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1Division of Nephrology and Hypertension, University of California, Irvine, Irvine, CA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Association of malnutrition-inflammation complex and responsiveness to erythropoiesis-stimulating ag...
Next Document: High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease.