Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients

Aida Collado; Elena Domingo; Patrice Marques; Eva Perello; Sergio Martínez-Hervás; Laura Piqueras; Juan F Ascaso; José T Real; Maria-Jesus Sanz

doi:10.3389/fphar.2021.656244

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients

Front Pharmacol. 2021 Apr 20:12:656244. doi: 10.3389/fphar.2021.656244. eCollection 2021.

Authors

Aida Collado^{1

2}, Elena Domingo¹, Patrice Marques^{1

2}, Eva Perello^{2

3}, Sergio Martínez-Hervás^{2

3

4}, Laura Piqueras^{1

2

3}, Juan F Ascaso^{2

3

4}, José T Real^{2

3

4}, Maria-Jesus Sanz^{1

2

3}

Affiliations

¹ Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain.
² Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain.
³ CIBERDEM-Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders, Carlos III Health Institute, Madrid, Spain.
⁴ Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain.

Abstract

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting. Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state. Design: A commercial liquid preparation of long-chain triglycerides (Supracal^®; ω6/ω3 ratio >20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after administration (postprandial state). Flow cytometry was employed to determine platelet and leukocyte activation, and the levels of circulating platelet-leukocyte aggregates. Soluble markers were determined by ELISA, and the parallel-plate flow chamber was employed to study leukocyte adhesion to the dysfunctional arterial endothelium. Results: The PH group had a lower percentage of activated platelets and circulating type 1 monocytes, and blunted neutrophil activation after the OUFL, accompanied by a significant increase in the percentage of regulatory T lymphocytes. In this group, the OUFL led to a significant impairment of leukocyte adhesion to the dysfunctional [tumor necrosis factor α (TNFα)-stimulated] endothelium and reduced the plasma levels of soluble P-selectin, platelet factor-4 (PF-4)/CXCL4, CXCL8, CCL2, CCL5, and TNFα. Conclusion: The OUFL has a beneficial impact on the pro-thrombotic and pro-inflammatory state of PH patients and might be a promising macronutrient approach to dampen the systemic inflammation associated with PH and the development of further cardiovascular events.

Keywords: endothelial dysfunction; inflammatory mediators; leukocytes; oral unsaturated fat load; platelet activation; primary hypercholesterolemia; systemic inflammation.