Document Detail

Aluminum-induced mitochondrial dysfunction leads to lipid accumulation in human hepatocytes: a link to obesity.
MedLine Citation:
PMID:  17762189     Owner:  NLM     Status:  MEDLINE    
Mitochondrial dysfunction is the cause of a variety of pathologies associated with high energy-requiring tissues like the brain and muscles. Here we show that aluminum (Al) perturbs oxidative-ATP production in human hepatocytes (HepG2 cells). This Al-induced mitochondrial dysfunction promotes enhanced lipogenesis and the accumulation of the very low density lipoprotein (VLDL). Al-stressed HepG2 cells secreted more cholesterol, lipids and proteins than control cells. The level of apolipoprotein B-100 (ApoB-100) was markedly increased in the culture medium of the cells exposed to Al. (13)C-NMR and HPLC studies revealed a metabolic profile favouring lipid production and lowered ATP synthesis in Al-treated cells. Electrophoretic and immunoblot analyses pointed to increased activities and expression of lipogenic enzymes such as glycerol 3-phosphate dehydrogenase (G3PDH), acetyl CoA carboxylase (ACC) and ATP-citrate lyase (CL) in the hepatocytes exposed to Al, and a sharp diminution of enzymes mediating oxidative phosphorylation. D-Fructose elicited the maximal secretion of VLDL in the Al-challenged cells. These results suggest that the Al-evoked metabolic shift favours the accumulation of lipids at the expense of oxidative energy production in hepatocytes.
Ryan Mailloux; Joseph Lemire; Vasu Appanna
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  20     ISSN:  1015-8987     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2007  
Date Detail:
Created Date:  2007-08-31     Completed Date:  2007-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  627-38     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2007 S. Karger AG, Basel.
Department of Chemistry and Biochemistry, Laurentian University, Ontario, Canada.
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MeSH Terms
Adenosine Triphosphate / biosynthesis
Aluminum / pharmacology*
Cell Line, Tumor
Glucose / metabolism
Hepatocytes / drug effects*,  metabolism*,  secretion
Hydrogen Peroxide / pharmacology
Lipid Metabolism*
Magnetic Resonance Spectroscopy
Mitochondria / drug effects*,  metabolism*
Obesity / metabolism
Phosphotungstic Acid / pharmacology
Zinc / pharmacology
Reg. No./Substance:
12067-99-1/Phosphotungstic Acid; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 7429-90-5/Aluminum; 7440-66-6/Zinc; 7722-84-1/Hydrogen Peroxide

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