Abstract 15228: Identification of a Novel Regulatory Pathway for Acyl-CoA Synthetase 1 Expression by Cholesterol Through Tissue Profiling in Cholesterol- Fed Hamsters
Authors: Amar B. Singh, Chin Fung Kelvin Kan, Bin Dong, Jingwen Liu
Journal: Circulation (2013)

Abstracts and presentations are embargoed for release at date and time ofpresentation or time of AHA/ASA news event. Information may not be releasedbefore then. Failure to honor embargo policies will result in the abstract beingwithdrawn and barred from presentation. Core 2. Epidemiology and Prevention of CV Disease: Physiology,Pharmacology and Lifestyle Session Title: Nutrition in CVD Risk: Basic Aspects Abstract 15228: Identification of a Novel RegulatoryPathway for Acyl-CoA Synthetase 1 Expression byCholesterol Through Tissue Profiling in Cholesterol-Fed Hamsters Amar B Singh; Chin Fung Kelvin Kan; Bin Dong; Jingwen Liu Rsch Service, Palo Alto VA Health Care System, Palo Alto, CA Long-chain acyl-CoA synthetases (ACSL) play key roles in fatty acid utilization inall metabolic tissues including heart. Among the 5 ACSL isoforms, ACSL1 is themost abundant one in heart, liver and adipose tissue. Functional studies haverevealed a pivotal role of ACSL1 in FA β-oxidation in cardiac and adipose tissues.However, in liver, ACSL1 absence only resulted in small changes in FAcompositions of phospholipids and slight reductions in TAG synthesis. Further toACSL1’s divergent functions in different tissues, its regulation exhibits tissue-specificity. In heart, liver and adipose tissue, ACSL1 expression is elevated byPPARα ligand. In microphages, ACSL1 expression is highly induced byproinflammatory cytokines but does not respond to PPAR activation. Over the pastseveral years, evidence is accumulating to support the notion that the upstreamregulatory signaling pathways of different ACSL isoforms impact their tissue-specific functions in channeling FA into different metabolic pathways to meet thebody’s energy demand. To gain a deeper understanding of the regulation of ACSL1under different nutritional status, we first cloned ACSL1 homolog of golden Syrianhamster; next we tissue profiled ACSL1 mRNA and protein expressions in hamstersfed a normal diet (ND), a high fat diet (HF) or a high cholesterol diet (HC). Ourstudy shows that while HF diet had little effects on ACSL1 expression in variousorgans, HC diet downregulated ACSL1 mRNA and protein levels coordinately in atissue-specific manner. In testis, amounts of ACSL1 mRNA and protein in HCgroup were reduced to 25% and 37% of the ND group, respectively. In liver, HC dietlowered ACSL1 mRNA by 41% and protein by 55% as compared to the ND group. Inheart and brain, the negative effects of cholesterol on ACSL1 expression were alsosignificant albeit to lesser extents as compared to testis and liver. Interestingly,the expression of ACSL1 mRNA and protein in adipose tissue and skeletal musclewere unchanged by HC diet. Collectively, our study identifies a novel regulatorypathway utilized by cholesterol that modulates ACSL1 cellular abundance in atissue-specific manner. This work shed new light on the functional role of ACSL1in hypercholesterolemia, the underlying cause of cardiovascular disease.Author Disclosures: A.B. Singh: None. C. Kan: None. B. Dong: None. J. Liu: None.Key Words: Gene expression • Lipids • Nutrition • Cardiovascular disease • Diet