Comparative Analyses of Disease Risk Genes Belonging to the Acyl-CoA Synthetase Medium-Chain (ACSM) Family in Human Liver and Cell Lines

Abstract

The human ACSM1, 2A and B, 3, and 5 genes, located on chromosome 16p12-13, encode for enzymes catalyzing the activation of medium-chain length fatty acids. Association studies have linked several polymorphisms of these genes to traits of insulin resistance syndrome. In our study, ACSM transcripts showed 3 to >400-fold higher expression levels in human liver when compared to cell lines by qRT-PCR. This difference was also evident at the protein level, as shown for ACSM2. In liver, ACSM2 was the most abundant transcript, showing sixfold (vs. ACSM3) to >300-fold higher expression levels (vs. ACSM1). Mitochondrial localization of the ACSM2 protein and the presence of an N-terminal targeting sequence were shown by GFP-tagging. We have shown ACSM2B to be the predominant transcript in human liver, and genetic variations of this gene could therefore play an important role in disease susceptibility.

RNA-Seq Based Transcriptome Analysis of Hepatitis E Virus (HEV) and Hepatitis B Virus (HBV) Replicon Transfected Huh-7 Cells

“…Acyl-CoA Synthetase Medium-Chain Family Member 1 (ACSM1, down regulated) is a fatty acid CoA ligase catalyzing the activation of medium chain fatty acids for mitochondrial beta-oxidation (Table S5). Its down regulation might contribute to steatosis, however as two other members of this family i.e., ACSM2 and ACSM3 show higher expression levels in hepatocytes [63], the significance of this alteration is uncertain. Another Acyl CoA synthetase, ACSBG1 (bubblegum family member 1, also known as lipidosin) was found to be down regulated in HEV-only group (Table S5).…”

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

“…Localization of medium-chain acyl-CoA synthetase in the mitochondrial matrix was first described in the late 60s of the past century (79) [for more recent reports see (80,81)]. The latter property may have important metabolic consequences under specific conditions, as will be discussed further.…”

Effect of the non-steroidal anti-inflammatory drugs on the acyl-CoA synthetase activity toward medium-chain, long-chain and polyunsaturated fatty acids in mitochondria of mouse liver and brain

“…The expression levels of the isoforms of the long-chain acyl-CoA synthetases in the brain and liver remain fully unknown. However, there are the reports that the abundant expression of mRNA of the long-chain acylCoA synthetases 1, 4 and 5 was detected in rat liver [33][34][35] , whereas that of long-chain acyl-CoA synthetases 3 and 6 was detected in rat brain [33][34][35] . Second, there are five longchain acyl-CoA synthetases overlapping the substrate specificities 34 .…”