Document Detail

Nordihydroguaiaretic acid improves metabolic dysregulation and aberrant hepatic lipid metabolism in mice by both PPARα-dependent and -independent pathways.
MedLine Citation:
PMID:  23104557     Owner:  NLM     Status:  MEDLINE    
Creosote bush-derived nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, possesses antioxidant properties and functions as a potent antihyperlipidemic agent in rodent models. Here, we examined the effect of chronic NDGA treatment of ob/ob mice on plasma dyslipidemia, hepatic steatosis, and changes in hepatic gene expression. Feeding ob/ob mice a chow diet supplemented with either low (0.83 g/kg diet) or high-dose (2.5 g/kg diet) NDGA for 16 wk significantly improved plasma triglyceride (TG), inflammatory chemokine levels, hyperinsulinemia, insulin sensitivity, and glucose intolerance. NDGA treatment caused a marked reduction in liver weight and TG content, while enhancing rates of fatty acid oxidation. Microarray analysis of hepatic gene expression demonstrated that NDGA treatment altered genes for lipid metabolism, with genes involved in fatty acid catabolism most significantly increased. NDGA upregulated the mRNA and nuclear protein levels of peroxisome proliferator-activated receptor α (PPARα), and the activated (phosphorylated) form of AMP-activated kinase. NDGA increased PPARα promoter activity in AML12 hepatocytes and also prevented the fatty acid suppression of PPARα expression. In contrast, PPARα siRNA abrogated the stimulatory effect of NDGA on fatty acid catabolism. Likewise, no stimulatory effect of NDGA on hepatic fatty acid oxidation was observed in the livers of PPARα-deficient mice, but the ability of NDGA to reverse fatty liver conditions was unaffected. In conclusion, the beneficial actions of NDGA on dyslipidemia and hepatic steatosis in ob/ob mice are exerted primarily through enhanced fatty acid oxidation via PPARα-dependent pathways. However, PPARα-independent pathways also contribute to NDGA's action to ameliorate hepatic steatosis.
Haiyan Zhang; Wen-Jun Shen; Yuan Cortez; Fredric B Kraemer; Salman Azhar
Related Documents :
16548537 - Novel lipid system forming hollow microtubes at high yields and concentration.
73337 - Cytochemical identification of oxalosuccinic acid in human leukocytes.
1182127 - Surface and solution properties of steroid antibiotics: 3-acetoxylfusidic acid, cephalo...
15717227 - Changes in fatty acid composition of chromohalobacter israelensis with varying salt con...
6438097 - Secretogogue-stimulated phosphatidylinositol breakdown in the exocrine pancreas liberat...
6793027 - The rate of absorption of synthetic lysine and dietary protein in the upper half of the...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-10-25
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  304     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-02-20     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G72-86     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adipokines / metabolism
Endoplasmic Reticulum Stress / physiology
Endoribonucleases / metabolism
Fatty Acids / metabolism
Fatty Liver / drug therapy
Glucose Tolerance Test
Hypolipidemic Agents / therapeutic use*
Leptin / deficiency
Lipid Metabolism / genetics
Lipid Metabolism Disorders / drug therapy*
Lipoproteins, VLDL / metabolism
Lipoxygenase Inhibitors / therapeutic use*
Liver / drug effects,  metabolism*
Masoprocol / therapeutic use*
Mice, Inbred C57BL
Mice, Knockout
Microarray Analysis
Multigene Family
PPAR alpha / physiology*
Protein-Serine-Threonine Kinases / metabolism
Real-Time Polymerase Chain Reaction
Signal Transduction / drug effects
Triglycerides / biosynthesis
Grant Support
Reg. No./Substance:
0/Adipokines; 0/Fatty Acids; 0/Hypolipidemic Agents; 0/Leptin; 0/Lipoproteins, VLDL; 0/Lipoxygenase Inhibitors; 0/PPAR alpha; 0/Triglycerides; 7BO8G1BYQU/Masoprocol; EC protein, mouse; EC Kinases; EC 3.1.-/Endoribonucleases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes?
Next Document:  Complement depletion protects lupus-prone mice from ischemia reperfusion-initiated organ injury.