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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #353351
Title: Oxylipins in triglyceride-rich lipoproteins of dyslipidemic subjects promote endothelial inflammation following a high fat meal

Author
item RAJAMANI, ANITA - University Of California, Davis
item BORKOWSKI, KAMIL - University Of California, Davis
item AKRE, SAMIR - University Of California, Davis
item FERNANDEZ, ANDREA - University Of California, Davis
item Newman, John
item SIMON, SCOTT - University Of California, Davis
item PASSERINI, ANTHONY - University Of California, Davis

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2019
Publication Date: 6/17/2019
Citation: Rajamani, A., Borkowski, K., Akre, S., Fernandez, A., Newman, J.W., Simon, S.I., Passerini, A.G. 2019. Oxylipins in triglyceride-rich lipoproteins of dyslipidemic subjects promote endothelial inflammation following a high fat meal. Scientific Reports. 9:8655. https://doi.org/10.1038/s41598-019-45005-5.
DOI: https://doi.org/10.1038/s41598-019-45005-5

Interpretive Summary: Elevated levels of triglyceride-rich lipoproteins (TGRL) in the plasma promotes atherosclerosis in humans. This study investigates whether the TGRL composition of polyunsaturated fatty acids and their bioactive oxygenated metabolites (i.e. oxylipins) are altered in response to a high saturated fat meal in proportion to an individual’s fasting cardiometabolic risk factors. Moreover, we evaluated if the abundance of these lipids and their metabolites correlated with an inflammatory response of cultured vascular endothelial cells exposed to TGRLs. For this, we isolated TGRL from subject plasma at fasting and 3.5 h after eating (i.e. postprandial) a high saturated fat test meal. Human aortic endothelial cells were stimulated with the inflammatory cytokine TNFa (0.3 ng/ml) and treated with postprandial TGRL (10 mg/dl ApoB) for 4hrs to initiate an inflammatory response. Changes in the surface expression of vascular cellular adhesion molecule 1 (VCAM-1) were quantified by flow cytometry and correlated with plasma lipid markers. Concentrations of esterified and non-esterified fatty acids and oxylipins were measured by mass spectrometry in isolated TGRL from both the fasting and fed state. Oxylipin profiles distinguished postprandial TGRL-dependent priming of either a pro- or anti-atherogenic response, characterized by a =35% increase or =15% decrease in VCAM-1 expression respectively. Pro-atherogenic TGRL were enriched in fatty acids with alcohols on neighboring carbons (i.e. vicinal-diols), and single alcohols in the middle of the fatty acid chain. The non-esterified linoleate-derived 9-HODE and esterified alpha-linolenate-derived 9,10-DiHODE showing the strongest correlation with change in VCAM-1 expression. This study links changes in TGRL composition with endothelial VCAM-1 expression that marks among the earliest changes in atherosclerosis.

Technical Abstract: Triglyceride-rich lipoproteins (TGRL) promote atherosclerosis. This study investigates whether TGRL composition of PUFA and their oxygenated metabolites (i.e. oxylipins) are altered in response to a high saturated fat meal in proportion to an individual’s fasting cardiometabolic risk factors, and if their abundance correlates with endothelial cell inflammatory responses to TGRL exposure. For this, we isolated TGRL from subject plasma at fasting and 3.5 h postprandial to a high saturated fat test meal exposure. Human aortic endothelial cells were stimulated with TNFa (0.3 ng/ml) and treated with postprandial TGRL (10 mg/dl ApoB) for 4hrs. Changes in VCAM-1 surface expression relative to TNFa were quantified by flow cytometry and correlated with plasma lipid markers. Concentrations of esterified and non-esterified FA and oxylipins were measured by UPLC-MS/MS mass spectrometry in fasting and postprandial TGRL (n=10). Oxylipin profiles distinguished postprandial TGRL priming a pro- or anti-atherogenic response, characterized by an increase (=35%) or decrease (=15%) in VCAM-1 respectively. Pro-atherogenic TGRL were enriched in vicinal (1,2)-diols and mid-chain alcohols, with non-esterified 9-HODE and esterified 9,10-DiHODE showing the strongest correlation with change in VCAM-1 expression. This study links changes in TGRL composition with endothelial VCAM-1 expression that marks among the earliest changes in atherosclerosis