| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Haiyan Zhang; Wen-Jun Shen; Yuan Cortez; Fredric B Kraemer; Salman Azhar |
Related Documents
:
|
17709127 - Impact of feed water acidification with weak and strong acids on colloidal silica fouli... 23051667 - Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid... 7073957 - The effect of culture media on the production and measurement of luminol-dependent chem... 23542747 - In vitro response of putative fatty acid-sensing systems in rainbow trout liver to incr... 4022907 - Fatty acid compositions of triacylglycerols and phospholipids in hen liver lipid before... 1908767 - Changes in plasma and urinary amino acid levels during diabetic ketoacidosis in children. |
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: 2013-04-16 |
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 |
Affiliation:
|
Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adipokines
/
metabolism Animals Diet 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* Male Mice Mice, Inbred C57BL Mice, Knockout Microarray Analysis Multigene Family Nordihydroguaiaretic Acid / therapeutic use* PPAR alpha / physiology* Protein-Serine-Threonine Kinases / metabolism Real-Time Polymerase Chain Reaction Signal Transduction / drug effects Triglycerides / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
|
1R01HL92473/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Adipokines; 0/Fatty Acids; 0/Hypolipidemic Agents; 0/Leptin; 0/Lipoproteins, VLDL; 0/Lipoxygenase Inhibitors; 0/PPAR alpha; 0/Triglycerides; 500-38-9/Nordihydroguaiaretic Acid; EC 2.7.11.1/Ern1 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine 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.