Grant: Project Grant

Omega-3 (n-3) fats from fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may help prevent cardiovascular diseases (CVDs), but recent evidence is not clear. Furthermore, obesity helps drive CVDs to be a leading cause of death worldwide, and is more common in men than women. EPA may reduce CVD risk in men but not women, while supplementing EPA with DHA may provide no benefits. We have shown that DHA prevents EPA from being converted to other molecules that may help prevent CVD. Our studies are designed to address this potentially important finding. Our objective is to determine how obesity affects liver and heart n-3 fat metabolism and atherosclerosis (plaque buildup) when mice are fed alpha-linolenic acid (ALA, n-3 fat from plants), EPA or EPA+DHA. Specifically, we aim to: 1.Determine DHA synthesis rates in male and female obese and lean mice. 2.Measure how the liver and heart metabolize n-3 fats on obese and lean mice following different n-3 dietary fat combinations. 3.Determine the effect of n-3 fat intake levels and combinations on atherosclerosis First, we will feed mice low- and high-fat diets to induce obesity, containing varying levels of ALA, EPA or EPA+DHA over many weeks. After switching to 'labeled' ALA, EPA or DHA, we will track the fate of ALA, EPA and DHA and determine effects of altered n-3 fat metabolism on inflammation, with particular focus in the liver and heart. Second, we will feed different levels of EPA and EPA+DHA to atherosclerotic mice to assess the role that dose of the dietary n-3 fat plays on protection against atherosclerosis. To measure this, we will image atherosclerotic plaque size, and measure corresponding levels of inflammation in the heart and other tissues. By measuring n-3 fat metabolism and atherosclerosis, our animal research will provide metabolic insight and potential explanations for the observed differences in the CVD protection of EPA supplementation, but not DHA supplementation, in humans.