N‐3 Fatty Acids Decrease LDL‐Cholesterol Delivery and Lipoprotein Lipase in the Arterial Wall in Insulin Resistant Mice

Abstract

We reported that saturated fat enriched diets (SAT) increase arterial LDL‐cholesteryl ester (CE) deposition from LDL selective uptake (SU) ‐ a process of LDL‐CE uptake without concomitant uptake of whole particle, and this was associated with increased arterial lipoprotein lipase (LpL) levels. We now questioned how n‐3 fatty acid (n‐3 FA) rich diets influence arterial cholesterol (Ch) delivery and LpL levels. Mixed‐background rescued insulin receptor knockout mice were used as an insulin resistant (IR) model and fed chow or high fat diets enriched in n‐3 or SAT for 12 wk, followed by bolus injection of fluorescent BODIPY‐CE and Alexa labeled human LDL to independently trace LDL‐CE and ‐apoB/whole particle uptake. In contrast to SAT, n‐3 diets markedly reduced all plasma lipids (p<0.05), ameliorating IR. As opposed to SAT, n‐3 reduced arterial LDL uptake, CE deposition and SU (1.12±0.14, 2.94±0.17, n‐3 vs. SAT, p<0.05). Disparate patterns of CE deposition between diets were comparable with arterial LpL distributions; SAT induced high LpL throughout aortic media; LpL was limited to intima only in n‐3 mice. These studies indicate dietary n‐3 FA reduces arterial LDL‐Ch delivery and deposition with changing arterial LpL levels and distribution. We hypothesize one mechanism whereby n‐3 FA diminishes adverse cardiovascular disease outcomes in IR, is by diminishing arterial LDL‐Ch deposition early in atherogenesis.Grant Funding SourceNIH grant T32‐DK007647‐18