Abstract
Long-chain fatty acyl-CoA synthetase (ACSLs) is an essential enzyme for the synthesis of fatty acyl-CoA. ACSL1 plays a key role in the synthesis of triglycerides, phospholipids, and cholesterol esters. Background: In the current study, triglyceride content did not increase after overexpression of the ACSL1 gene. Methods: RNA-seq and lipid metabolome profiling were performed to determine why triglyceride levels did not change with ACSL1 overexpression. Results: Fatty acyl-CoA produced by ACSL1 was determined to be involved in the diglyceride synthesis pathway, and diglyceride content significantly increased when ACSL1 was overexpressed. Moreover, the arachidonic acid (AA) content in sheep adipocytes significantly increased, and the level of cyclooxygenase 2 (COX2) expression, the downstream metabolic gene, was significantly downregulated. Knocking down the ACSL1 gene was associated with an increase in COX2 mRNA expression, as well as an increase in prostaglandin content, which is the downstream metabolite of AA. Conclusions: The overexpression of the ACSL1 gene promotes the production of AA via downregulation of COX2 gene expression.
Highlights
Long-chain fatty acyl-CoA synthetases (ACSLs) are essential for fatty acid (FA) activation and catalysis
The expression of ACSL1 mRNA in sheep adipocytes significantly increased during the process of inducing differentiation on days 0, 4, and 8 (Figure 1b), and protein expression significantly increased on day 8 (Figure 1c)
These findings demonstrate that ACSL1-overexpressing preadipocytes were successfully generated
Summary
Long-chain fatty acyl-CoA synthetases (ACSLs) are essential for fatty acid (FA) activation and catalysis. ACSL1 is involved in the synthesis of triglycerides from fatty acyl-CoA, promotes the deposition of FAs [3], activates FA, and enters the β-oxidation pathway [4]. FA oxidation levels in white adipocytes decrease, and cold tolerance is low in ACSL1 knockout mice, indicating that ACSL1 plays an important role in the activation of FA oxidation [12] These studies suggest that the level of ACSL1 in tissues may be related to FA metabolism. After the cells were allowed to differentiate for eight days, and cellular triglyceride content was measured, the triglyceride content in the treated cells did not significantly differ from the control cells This result is in contrast to what was previously known about the role of the ACSL1 gene in lipid metabolism [1,2,7]. To further determine the effect of ACSL1 on sheep adipocytes, a combined transcriptome and metabolome analysis was performed
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