Dietary Fatty Acid Saturation Modulates Sphingosine-1-Phosphate-Mediated Vascular Function

Daniel W Nuno,Kathryn G Lamping

doi:10.1155/2019/2354274

Abstract

Sphingolipids, modified by dietary fatty acids, are integral components of plasma membrane and caveolae that are also vasoactive compounds. We hypothesized that dietary fatty acid saturation affects vasoconstriction to sphingosine-1-phosphate (S1P) through caveolar regulation of rho kinase. Wild type (WT) and caveolin-1-deficient (cav-1 KO) mice which lack vascular caveolae were fed a low-fat diet (LF), 60% high-saturated fat diet (lard, HF), or 60% fat diet with equal amounts of lard and n-3 polyunsaturated menhaden oil (MO). Weight gain of WT on HF and MO diets was similar while markedly blunted in cav-1 KO. Neither high-fat diet affected the expression of cav-1, rho, or rho kinase in arteries from WT. In cav-1 KO, MO increased the vascular expression of rho but had no effect on rho kinase. HF had no effect on rho or rho kinase expression in cav-1 KO. S1P produced a concentration-dependent constriction of gracilis arteries from WT on LF that was reduced with HF and restored to normal with MO. Constriction to S1P was reduced in cav-1 KO and no longer affected by a high-saturated fat diet. Inhibition of rho kinase which reduced constriction to PE independent of diet in arteries from WT and cav-1 KO only reduced constriction to S1P in arteries from WT fed MO. The data suggest that dietary fatty acids modify vascular responses to S1P by a caveolar-dependent mechanism which is enhanced by dietary n-3 polyunsaturated fats.

Highlights

Poor diet composition is a major contributor to the epidemic of overweight and obese individuals who are at an increased risk of developing type 2 diabetes and cardiovascular disease
To determine whether a change in dietary fatty acids reverses the effects of HF diet, after 12 weeks of HF diet, random groups of HF mice were switched to a 60% high diet with half of the lard replaced with n-3 polyunsaturated fatty acids (PUFA)-enriched menhaden oil (MO, Research Diets, D10122003)
Body weight of cav-1 KO mice on normal low-fat diet (LF) diet was similar to Wild type (WT) but neither high-fat diet increased body weight of cav1 KO to the levels of WT (Figure 1(a))

Summary

Introduction

Poor diet composition is a major contributor to the epidemic of overweight and obese individuals who are at an increased risk of developing type 2 diabetes and cardiovascular disease. While abnormal levels of triglycerides, free fatty acids, and cholesterol contribute to dyslipidemia, other lipid species are generated with high-fat diets which could contribute to development of vascular disease. The sphingolipid ceramide produced in all tissues is elevated with a high-saturated fat diet, hypertension, type 2 diabetes, and insulin resistance [1,2,3,4,5,6]. Levels of S1P are increased in genetic and diet-induced animal models of obesity and humans with obesity, atherosclerosis, and cardiovascular disease and can affect vascular function [9,10,11,12,13]. The impact of dietary fatty acids differing in the saturation level on S1P and vascular function has not been addressed

Methods

Results

Conclusion