Walnut Inclusion In A Palm-Based High-Fat And High-Cholesterol Diet Without Changing Total Energy Supply Stabilises Advanced Atheroma Plaque Through An Anti-Inflammatory Mechanism In Apoe-Deficient Mice

Aims: The North-to-South gradient in cardiovascular disease in Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques (responsible for most culprit lesions) in Southern Europe. Consumption of certain foods delays atherosclerosis progression. In a mouse model of accelerated atherosclerosis we investigated whether the inclusion of walnuts within an atherogenic diet stabilizes advanced atheroma plaque.Methods: Apolipoprotein E-deficient mice (male, 10-week old) were randomized to receive either a control diet (9.6% of energy as fat, n=14), a palm oil-based high-fat diet (40% of energy as fat, n=15) or an isocaloric diet which fat was partially supplied by walnuts, in a dose equivalent to 30 g/d in humans (n=14). All diets contained 0.2% cholesterol. After 15 weeks of intervention, we evaluated changes in aortic atherosclerotic lesions (size and composition) and expression levels of markers for inflammation and oxidative stress. Results: There were no among-group differences in atherosclerotic size and extension, or oxidative stress. Compared to control diet, palm oil-diet induced plaque instability (higher lipid and necrosis, and lower collagen-to-lipid ratio). Walnut inclusion attenuated these features and decreased macrophage infiltration. Palm oil-based diet increased expression of chemokines, cytokines, inflammasome, and M1-macrophage marker compared to control diet. Such response was not observed in walnut group. Findings for walnut group could be explained by the differential aortic activation of NFkB (down-regulated) and Nrf2 (up-regulated). Conclusions: Isocaloric inclusion of walnuts in an unhealthy high-fat diet stabilizes advanced atheroma plaque. This contributes novel mechanistic evidence for the cardiovascular benefits of walnuts.