Intestinal lipid transport and chylomicron production: Possible links to exacerbated atherogenesis in a rodent model of the metabolic syndrome

Abstract

Post-prandial lipaemia is prevalent during conditions of obesity and insulin-resistance (IR), and has been associated with mediating the accelerated progression of cardiovascular disease (CVD). Our group has contributed to the concept that intestinally derived chylomicron lipoproteins are atherogenic and are associated with increased cholesterol accumulation in arterial vessels. More recently we have established the JCR:LA- cp rodent model of post-prandial dyslipidemia during conditions of the metabolic syndrome (MetS): including obesity, insulin-resistance and intimal atherogenesis. We have used this model as a novel physiological approach to investigate intestinal lipid transport and metabolism in the ‘absorption-to-chylomicron secretion’ axis, in the context of IR. The purpose of this review is to highlight recent preliminary data that has been collected using a range of different methodologies in this unique model of MetS. For the first time we report that the JCR:LA- cp rodent has over-production of intestinal chylomicrons and that this is associated with intestinal villus hypertrophy. We have also observed that vascular re-modelling associated with increased arterial accumulation of atherogenic lipoproteins is evident in this model. We discuss our findings in the context of a void of knowledge in the understanding of intestinal lipid metabolism, and the potential significance of these pathways in contributing to dyslipidemia in MetS.