The Role of Palmitic Acid in the Co-Toxicity of Bacterial Metabolites to Endothelial Cells

• Published in: Vascular health and risk management Vol. 19; pp. 399 - 409
• Main Authors: Choroszy, Marcin, Środa-Pomianek, Kamila, Wawrzyńska, Magdalena, Chmielarz, Mateusz, Bożemska, Edyta, Sobieszczańska, Beata
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2023; Dove; Dove Medical Press
• Subjects: Atherosclerosis; E-Selectin; Endothelium; Endothelium, Vascular; Endotoxemia - metabolism; endotoxin; high-fat diet; Human Umbilical Vein Endothelial Cells - metabolism; Humans; indoxyl sulfate; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; metabolic endotoxemia; Metabolites; Muscle proteins; Nitric oxide; Obesity; Occludin - metabolism; Occludin - pharmacology; Original Research; palmitic acid; Palmitic Acid - metabolism; Palmitic Acid - toxicity; Permeability; Physiological aspects; Saturated fatty acids; Sulfates; Vascular Cell Adhesion Molecule-1 - metabolism; Vascular Cell Adhesion Molecule-1 - pharmacology; Poland; indoxyl sulfate; palmitic acid; high-fat diet; endotoxin; metabolic endotoxemia
• ISSN: 1178-2048; 1176-6344; 1178-2048
• DOI: 10.2147/VHRM.S408897

Metabolic endotoxemia most often results from obesity and is accompanied by an increase in the permeability of the intestinal epithelial barrier, allowing co-absorption of bacterial metabolites and diet-derived fatty acids into the bloodstream. A high-fat diet (HFD) leading to obesity is a significant extrinsic factor in developing vascular atherosclerosis. In this study, we evaluated the effects of palmitic acid (PA) as a representative of long-chain saturated fatty acids (LCSFA) commonly present in HFDs, along with endotoxin (LPS; lipopolysaccharide) and uremic toxin indoxyl sulfate (IS), on human vascular endothelial cells (HUVECs). HUVECs viability was measured based on tetrazolium salt metabolism, and cell morphology was assessed with fluorescein-phalloidin staining of cells' actin cytoskeleton. The effects of simultaneous treatment of endothelial cells with PA, LPS, and IS on nitro-oxidative stress in vascular cells were evaluated quantitatively with fluorescent probes. The expression of vascular cell adhesion molecule VCAM-1, E-selectin, and occludin, an essential tight junction protein, in HUVECs treated with these metabolites was evaluated in Western blot. PA, combined with LPS and IS, did not influence HUVECs viability but induced stress on actin fibers and focal adhesion complexes. Moreover, PA combined with LPS significantly enhanced reactive oxygen species (ROS) production in HUVECs but decreased nitric oxide (NO) generation. PA also considerably increased the expression of VCAM-1 and E-selectin in HUVECs treated with LPS or IS but decreased occludin expression. Palmitic acid enhances the toxic effect of metabolic endotoxemia on the vascular endothelium.