| Inhibition of long-chain acyl coenzyme A synthetases during fatty acid loading induces lipotoxicity in macrophages. | |
| | |
MedLine Citation:
|
PMID: 19679826 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: Obesity is often associated with hypertriglyceridemia and elevated free fatty acids (FFAs), which are independent risk factors for cardiovascular disease and diabetes. Although impairment of cholesterol homeostasis is known to induce toxicity in macrophages, the consequence of altered fatty acid homeostasis is not clear. METHODS AND RESULTS: Long-chain acyl CoA synthetases (ACSLs) play a critical role in fatty acid homeostasis by channeling fatty acids to diverse metabolic pools. We treated mouse peritoneal macrophages (MPMs) with VLDL or FFAs in the presence of triacsin C, an inhibitor of the 3 ACSL isoforms present in macrophages. Treatment of macrophages with VLDL and triacsin C resulted in reduced TG accumulation but increased intracellular FFA levels, which induced lipotoxicity characterized by apoptosis. Treatment of MPMs with the saturated fatty acid stearic acid in the presence of triacsin C increased intracellular stearic acid and induced apoptosis. Stromal vascular cells collected from high-fat diet-fed mice displayed foam cell morphology and exhibited increased mRNA levels of macrophage markers and ACSL1. Importantly, all of these changes were associated with increased FFA level in AT. CONCLUSIONS: Inhibition of ACSLs during fatty acid loading results in apoptosis via accumulation of FFAs. Our data have implications in understanding the consequences of dysregulated fatty acid metabolism in macrophages. |
| | |
Authors:
|
Viswanathan Saraswathi; Alyssa H Hasty |
Related Documents
:
|
6295506 - The regulatory role of spermine and fatty acid in the interaction of amp deaminase with... 1779056 - Ruminal synthesis, biohydrogenation, and digestibility of fatty acids by dairy cows. 14559106 - Role of nuclear receptors in the regulation of gene expression by dietary fatty acids (... 9420796 - Radionuclide assessment of myocardial fatty acid metabolism by pet and spect. 7591486 - N,n-dialkoxycarbonylamino acids from the sodium hydride-mediated reaction of alkyl chlo... 2187146 - Two precursors of the heat-stable enterotoxin of escherichia coli: evidence of extracel... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2009-08-13 |
Journal Detail:
|
Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Nov |
Date Detail:
|
Created Date: 2009-10-22 Completed Date: 2010-02-04 Revised Date: 2011-05-04 |
Medline Journal Info:
|
Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
|
Languages: eng Pagination: 1937-43 Citation Subset: IM |
Affiliation:
|
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis / drug effects, physiology Cell Survival Cells, Cultured Cholesterol, VLDL / metabolism, pharmacology Coenzyme A Ligases / antagonists & inhibitors*, metabolism Fatty Acids, Nonesterified / metabolism*, pharmacology Lipid Metabolism / drug effects, physiology* Macrophages, Peritoneal / drug effects, metabolism* Mice Sensitivity and Specificity Triazenes / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
|
HL089466/HL/NHLBI NIH HHS; R01 HL089466-03/HL/NHLBI NIH HHS; R01 HL089466-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cholesterol, VLDL; 0/Fatty Acids, Nonesterified; 0/Triazenes; 76896-80-5/triacsin C; EC 6.2.1.-/Coenzyme A Ligases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Stability and aggregation of ranked gene lists.
Next Document: Statins block calcific nodule formation of valvular interstitial cells by inhibiting alpha-smooth mu...