Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet

Abstract

Distinct isoforms of long-chain acyl-CoA synthetases (ACSLs) may partition fatty acids toward specific metabolic cellular pathways. For each of the five members of the rat ACSL family, we analyzed tissue mRNA distributions, and we correlated the mRNA, protein, and activity of ACSL1 and ACSL4 after fasting and refeeding a 69% sucrose diet. Not only did quantitative real-time PCR analyses reveal unique tissue expression patterns for each ACSL isoform, but expression varied markedly in different adipose depots. Fasting increased ACSL4 mRNA abundance in liver, muscle, and gonadal and inguinal adipose tissues, and refeeding decreased ACSL4 mRNA. A similar pattern was observed for ACSL1, but both fasting and refeeding decreased ACSL1 mRNA in gonadal adipose. Fasting also decreased ACSL3 and ACSL5 mRNAs in liver and ACSL6 mRNA in muscle. Surprisingly, in nearly every tissue measured, the effects of fasting and refeeding on the mRNA abundance of ACSL1 and ACSL4 were discordant with changes in protein abundance. These data suggest that the individual ACSL isoforms are distinctly regulated across tissues and show that mRNA expression may not provide useful information about isoform function. They further suggest that translational or posttranslational modifications are likely to contribute to the regulation of ACSL isoforms.-Mashek, D. G., L. O. Li, and R. A. Coleman. Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet.

Suppression of Long Chain Acyl-CoA Synthetase 3 Decreases Hepatic de Novo Fatty Acid Synthesis through Decreased Transcriptional Activity

“…Yao and Ye (18) found that ACSL3 mediates the synthesis of phosphatidylcholine that is necessary for the assembly of very low density lipoprotein in human hepatoma cell lines. Also recent animal studies demonstrated that expression of mRNA of ACSL3 was down-regulated in 48-h-fasted rats (16). Taken as a whole, these data strongly support a synthetic role of ACSL3 in energy metabolism.…”

“…ACSL3 has a broad range of substrate preferences toward C 16 -C 24 fatty acids (35,37). Although few studies have focused on the physiological function of ACSL3 (16,35), its localization on lipid droplets or endoplasmic reticulum membranes (31,32) suggests that this enzyme is likely involved in lipid synthesis. Proteomic analyses have revealed that ACSL3 is located on the surface of lipid droplets and is physically associated with lipid droplets fractions in 3T3-L1 adipocytes (32), human hepatocytes (31), and A431 human epithelial cells (38).…”

Diminished Acyl-CoA Synthetase Isoform 4 Activity in INS 832/13 Cells Reduces Cellular Epoxyeicosatrienoic Acid Levels and Results in Impaired Glucose-stimulated Insulin Secretion

“…Acsl4 Knockdown Reduced Both GSIS and FA-augmented GSIS-Given the substrate preference and tissue distribution of Acsl4 (32,33), we evaluated the effect of Acsl4 knockdown on insulin secretion. In the presence of various secretagogues, including glucose, specific fatty acids, and KCl, knockdown of Acsl4 expression significantly reduced insulin secretion (Fig.…”

SREBP2 Activation Induces Hepatic Long-chain Acyl-CoA Synthetase 1 (ACSL1) Expression in Vivo and in Vitro through a Sterol Regulatory Element (SRE) Motif of the ACSL1 C-promoter

“…ACSL1 is the abundant isoform in major metabolic tissues, including liver, heart, adipose, and muscle. Whereas in vitro studies carried out in different cell lines have reported similar as well as conflicting functions of ACSL1 in mediating FA oxidation, FA uptake, and triglyceride (TG) synthesis (9,11,13), recent animal studies with tissue-specific knock-out of Acsl1 revealed some definitive functions of this enzyme. In heart and adipose tissues, Acsl1 deficiency generated a profound decrease in FA oxidation without an impact on [ 14 C]oleate incorporation into TG or phospholipid (14,15).…”

“…These isoforms differ substantially in their substrate preference, tissue distribution, and subcellular compartmentation as well as in their responses to nutritional status (9), all of which contributes to the unique functions of each isoform in a particular tissue or a cell type.…”