Long-chain acyl-CoA synthetase 1 mediates the palmitic acid-induced inflammatory response in human aortic endothelial cells.

Long-chain acyl-CoA synthetase 1 mediates the palmitic acid-induced inflammatory response in human aortic endothelial cells. Am J Physiol Endocrinol Metab. 2020 Sep 21;: Authors: Ren G, Bhatnagar S, Hahn DJ, Kim JA Abstract Saturated fatty acid (SFA) induces pro-inflammatory response through a toll-like receptor (TLR)-mediated mechanism, which is associated with cardiometabolic diseases such as obesity, insulin resistance, and endothelial dysfunction. Consistent with this notion, TLR2 or TLR4 knock-out mice are protected from obesity-induced pro-inflammatory response and endothelial dysfunction. Although SFA causes endothelial dysfunction through TLR-mediated signaling pathways, the mechanisms underlying SFA-stimulated inflammatory response are not completely understood. To understand the pro-inflammatory response in vascular endothelial cells in high lipid conditions, we compared the pro-inflammatory responses stimulated by palmitic acid (PA) and other canonical TLR agonists (LPS, Pam3CSK4, orMALP2) in human aortic endothelial cells. The expression profiles of E-selectin and the signal transduction pathways stimulated by PA were distinct from those stimulated by canonical TLR agonists. Inhibition of long-chain acyl-CoA synthetases (ACSL) by a pharmacological inhibitor or knock-down of ACSL1 blunted the PA-stimulated, but not the LPS- or Pam3CSK4-stimulated pro-inflammatory responses. Furthermore, triacsin C restored the insulin-stim...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research