Department of Food and Nutrition, College of Engineering, Daegu University, Gyeongsan 38453, Republic of Korea.
J Microbiol Biotechnol. 2023 Dec 28;33(12):1563-1575. doi: 10.4014/jmb.2307.07018. Epub 2023 Aug 18.
Acyl-coenzyme A (CoA):diacylglycerol acyltransferase 2 (DGAT2) catalyzes the last stage of triacylglycerol (TAG) synthesis, a process that forms ester bonds with diacylglycerols (DAG) and fatty acyl-CoA substrates. The enzymatic role of has been studied in various biological species. Still, the full description of how channels fatty acids in skeletal myocytes and the consequence thereof in glucose uptake have yet to be well established. Therefore, this study explored the mediating role of in glucose uptake and fatty acid partitioning under short interfering ribonucleic acid (siRNA)-mediated knockdown conditions. Cells transfected with siRNA downregulated glucose transporter type 4 () messenger RNA (mRNA) expression and decreased the cellular uptake of [1-C]-labeled 2-deoxyglucose up to 24.3% ( < 0.05). Suppression of deteriorated insulininduced Akt phosphorylation. siRNA reduced [1-C]-labeled oleic acid incorporation into TAG, but increased the level of [1-C]-labeled free fatty acids at 3 h after initial fatty acid loading. In an experiment of chasing radioisotope-labeled fatty acids, suppression augmented the level of cellular free fatty acids. It decreased the level of re-esterification of free fatty acids to TAG by 67.6% during the chase period, and the remaining pulses of phospholipids and cholesteryl esters were decreased by 34.5% and 61%, respectively. Incorporating labeled fatty acids into beta-oxidation products increased in siRNA transfected cells without gene expression involving fatty acid oxidation. These results indicate that has regulatory function in glucose uptake, possibly through the reaction of TAG with endogenously released or recycled fatty acids.
酰基辅酶 A（CoA）：二酰基甘油酰基转移酶 2（DGAT2）催化甘油三酯（TAG）合成的最后阶段，该过程与二酰基甘油（DAG）和脂肪酸酰基辅酶 A 底物形成酯键。该酶在各种生物物种中的作用已经得到研究。然而，尚未充分阐明 DGAT2 如何在骨骼肌细胞中引导脂肪酸以及由此对葡萄糖摄取的影响。因此，本研究在短发夹 RNA（siRNA）介导的 DGAT2 敲低条件下，探讨了 DGAT2 在葡萄糖摄取和脂肪酸分配中的中介作用。用 siRNA 转染的细胞下调葡萄糖转运蛋白 4（GLUT4）信使 RNA（mRNA）的表达，并使[1-C]-标记的 2-脱氧葡萄糖的细胞摄取减少了 24.3%（<0.05）。DGAT2 的抑制作用恶化了胰岛素诱导的 Akt 磷酸化。siRNA 减少了[1-C]-标记的油酸掺入 TAG，但在初始脂肪酸加载后 3 小时增加了[1-C]-标记的游离脂肪酸水平。在放射性同位素标记脂肪酸追踪实验中，DGAT2 的抑制作用增加了细胞内游离脂肪酸的水平。它在追踪期间使游离脂肪酸重新酯化形成 TAG 的水平降低了 67.6%，并且剩余的磷脂和胆固醇酯脉冲分别降低了 34.5%和 61%。在不涉及脂肪酸氧化的基因表达的情况下，将标记的脂肪酸掺入β-氧化产物中，在转染 siRNA 的细胞中增加。这些结果表明，DGAT2 在葡萄糖摄取中具有调节作用，可能通过 TAG 与内源性释放或再循环的脂肪酸反应。
