Abstract
We tested whether dietary fatty acids alter membrane composition shifting localization of signaling pathways within caveolae to determine their role in vascular function. Wild type (WT) and caveolin‐1‐deficient mice (cav‐1 KO), required for vascular caveolae formation, were fed low fat (LF), high saturated fat (HF, 60% kcal from lard), or high‐fat diet with 50:50 lard and n‐3 polyunsaturated fatty acid‐enriched menhaden oil (MO). HF and MO increased body weight and fat in WT but had less effect in cav‐1 KO. MO increased unsaturated fatty acids and the unsaturation index of aorta from WT and cav‐1 KO. In LF WT aorta, endothelial nitric oxide synthase (eNOS) was localized to cav‐1‐enriched low‐density fractions which shifted to actin‐enriched high‐density fractions with acetylcholine (ACh). HF and MO shifted eNOS to high‐density fractions in WT aorta which was not affected by ACh. In cav‐1 KO aorta, eNOS was localized in low‐density non‐caveolar fractions but not shifted by ACh or diet. Inducible NOS and cyclooxygenase 1/2 were not localized in low‐density fractions or affected by diet, ACh or genotype. ACh‐induced dilation of gracilis arteries from HF WT was similar to dilation in LF but the NOS component was reduced. In WT and cav‐1 KO, dilation to ACh was enhanced by MO through increased role for NOS and cyclooxygenase. We conclude that dietary fats affect vascular fatty acid composition and membrane localization of eNOS but the contribution of eNOS and cyclooxygenase in ACh‐mediated vascular responses is independent of lipid rafts.
Highlights
Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
Body fat mass and %fat were less in menhaden oil (MO)-fed mice compared with high saturated fat (HF) but both were greater that low fat (LF) mice (WT 4.6 Æ 0.7 g, HF 20.0 Æ 0.5 g*, MO 16.4 Æ 0.3 g*#, *P < 0.05 vs. LF, #P < 0.05 vs. HF; %fat Fig. 1C, n = 4–7)
Lean body mass did not differ in Wild type (WT) mice on either high-fat diet which resulted in a reduction in the %lean in both groups compared to LF (LF 21.9 Æ 0.4 g, HF 24.0 Æ 0.6 g, MO 24.7 Æ 0.8 g, % lean Fig. 1D)
Summary
The health implications of excess weight and obesity which continue to increase world-wide include development of Type 2 diabetes and cardiovascular disease (Collaborators et al 2017). Obesity is primarily a consequence of increased fat mass following excess nutrient consumption often from a diet high in saturated fats. Optimizing dietary fat composition is a target for reducing obesity and its related disease burden, but the appropriate substitute for saturated fats in the diet is controversial. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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