Beijing Key Laboratory for Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling 136100, China.
Int J Mol Sci. 2020 Mar 17;21(6):2044. doi: 10.3390/ijms21062044.
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.
In the current study, triglyceride content did not increase after overexpression of the gene.
RNA-seq and lipid metabolome profiling were performed to determine why triglyceride levels did not change with overexpression.
Fatty acyl-CoA produced by ACSL1 was determined to be involved in the diglyceride synthesis pathway, and diglyceride content significantly increased when 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 gene was associated with an increase in mRNA expression, as well as an increase in prostaglandin content, which is the downstream metabolite of AA.
The overexpression of the ACSL1 gene promotes the production of AA via downregulation of COX2 gene expression.
长链脂肪酸辅酶 A 合成酶(ACSLs)是合成脂肪酸辅酶 A 的必需酶。ACSL1 在甘油三酯、磷脂和胆固醇酯的合成中起着关键作用。
在本研究中,基因的过表达并没有增加甘油三酯的含量。
进行 RNA-seq 和脂质代谢组学分析,以确定为什么甘油三酯水平没有随着基因的过表达而改变。
确定由 ACSL1 产生的脂肪酸辅酶 A 参与了二酰基甘油的合成途径,并且当过表达时,二酰基甘油的含量显著增加。此外,绵羊脂肪细胞中的花生四烯酸(AA)含量显著增加,下游代谢基因环氧化酶 2(COX2)的表达水平显著下调。敲低基因与 mRNA 表达的增加以及 AA 的下游代谢产物前列腺素含量的增加有关。
ACSL1 基因的过表达通过下调 COX2 基因的表达促进 AA 的产生。