Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Abstract

Purpose: High-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its atherogenic potential effect. We investigate the effect of a high fat diet administered continuously or intermittently on lipid homeostasis and onset of early stage coronary ATS. Methods: We investigated: control pigs receiving standard diet (C, n=7); pigs receiving a high-fat diet for ten weeks each day (CHF, n=5); pigs receiving high-fat diet every other week for ten weeks (IHF, n=7). Coronary angiography, intravascular ultrasound (IVUS) and Doppler flow measurements of the left anterior descending artery (LAD) were performed. Lipoproteins plasma composition, expression of genes involved in lipid homeostasis and histology of coronary samples were obtained. Results: In all CHF and IHF cases LAD lumen reduction was < 10% at IVUS and angiography with similar early ATS lesions at histology. As compared to CHF, IHF group showed a similar increase in total and LDL cholesterol but markedly higher HDL levels (p<0.0001). Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα with its target genes in the CHF group and in the IHF group while SREBP-2 was found significantly inhibited, as well as LDLr. A significant correlation was found between ABCA1 expression and circulating levels of HDL or ApoA1. Conclusions: Intermittent as compared to uninterrupted short term high fat diet decreases plasma LDL/HDL ratio. Periodic withdrawals of a high-fat atherogenic diet, compared to regular administration, results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL.