NDLI: Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways.

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Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bu, So Young Mashek, Douglas G.
Description	Country affiliation: United States Author Affiliation: Bu SY ( Department of Food Science and Nutrition, University of Minnesota, St Paul, MN, USA.)
Abstract	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- 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.
File Format	HTM / HTML
ISSN	00222275
e-ISSN	15397262
DOI	10.1194/jlr.M009407
Journal	The Journal of Lipid Research
Issue Number	11
Volume Number	51
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Biochemistry Coenzyme A Ligases Metabolism Fatty Acids Biosynthesis Liver Enzymology Metabolic Networks And Pathways Mitochondrial Proteins Animals Biological Transport Deficiency Genetics Esterification Gene Expression Regulation Gene Knockdown Techniques Hepatocytes Lipogenesis Oxidation-reduction Rna, Small Interfering Rats, Sprague-dawley Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Endocrinology

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