| Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways. | |
| | |
MedLine Citation:
|
PMID: 20798351 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Long-chain acyl-CoA synthetases (ACSLs) and fatty acid transport proteins (FATPs) activate fatty acids (FAs) to acyl-CoAs prior to their downstream metabolism. Of numerous ACSL and FATP isoforms, ACSL5 is expressed predominantly in tissues with high rates of triacylglycerol (TAG) synthesis, suggesting it may have an anabolic role in lipid metabolism. To characterize the role of ACSL5 in hepatic energy metabolism, we used small interference RNA (siRNA) to knock down ACSL5 in rat primary hepatocytes. Compared with cells transfected with control siRNA, suppression of ACSL5 expression significantly decreased FA-induced lipid droplet formation. These findings were further extended with metabolic labeling studies showing that ACSL5 knockdown resulted in decreased [1-(14)C]oleic acid or acetic acid incorporation into intracellular TAG, phospholipids, and cholesterol esters without altering FA uptake or lipogenic gene expression. ACSL5 knockdown also decreased hepatic TAG secretion proportionate to the observed decrease in neutral lipid synthesis. ACSL5 knockdown did not alter lipid turnover or mediate the effects of insulin on lipid metabolism. Hepatocytes treated with ACSL5 siRNA had increased rates of FA oxidation without changing PPAR-α activity and target gene expression. These results suggest that ACSL5 activates and channels FAs toward anabolic pathways and, therefore, is an important branch point in hepatic FA metabolism. |
| | |
Authors:
|
So Young Bu; Douglas G Mashek |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-26 |
Journal Detail:
|
Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-10-13 Completed Date: 2011-01-19 Revised Date: 2011-11-01 |
Medline Journal Info:
|
Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
|
Languages: eng Pagination: 3270-80 Citation Subset: IM |
Affiliation:
|
Department of Food Science and Nutrition, University of Minnesota, St Paul, MN, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Biological Transport Coenzyme A Ligases / deficiency, genetics, metabolism* Esterification / genetics Fatty Acids / biosynthesis*, metabolism* Gene Expression Regulation / genetics Gene Knockdown Techniques Hepatocytes / metabolism Lipogenesis / genetics Liver / enzymology*, metabolism Male Metabolic Networks and Pathways* / genetics Mitochondrial Proteins / deficiency, genetics, metabolism* Oxidation-Reduction RNA, Small Interfering / genetics Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids; 0/Mitochondrial Proteins; 0/RNA, Small Interfering; EC 6.2.1.-/Coenzyme A Ligases; EC 6.2.1.3/Acsl5 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering.
Next Document: Larry kricka.