Regulation and Impact of Cardiac Fatty Acid Uptake in Response to n-3 Fatty Acids (Abstract ID: 270971)

Alexander Dumas; Brandon Davies

doi:10.1016/j.jpet.2026.104798

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in the world with ~19.4 millions of deaths in 2021, an 18% increase from 2011. The incidence of cardiovascular risk and disease is predicted to continue climbing in the coming decades. The risk of CVD increases with metabolic conditions such as hypertriglyceridemia, diabetes, and obesity. Dietary omega-3 (n-3) poly-unsaturated fatty acids have gained popularity as a means of lowering circulating triglycerides and potentially reducing the risk for CVD. Increasing evidence from rodent and human studies have demonstrated that n-3s reduce circulating triglycerides and increase insulin sensitivity but only some human studies have found that n-3s reduce the risk of CVD. The heterogeneity found in these clinical studies suggests that our understanding of n-3s and their benefits is incomplete. Preliminary data in our lab shows that mice fed a fish oil diet (enriched in n-3s) had a striking increase in cardiac triglyceride-derived fatty acid uptake while also showing lowered plasma insulin levels and increased insulin sensitivity. This is intriguing as increased cardiac fatty acid uptake is commonly associated with increased risk of ischemic heart disease, stroke, and cardiomyopathy. Furthermore, these data suggest three interesting and important questions: 1) Is increased cardiac fatty acid uptake, under these conditions, beneficial or detrimental to heart health? 2) Does increased fatty acid uptake in the heart contribute to the increased systemic insulin sensitivity in mice on an n-3 based diet? 3) How does an n-3 enriched diet increase fatty acid uptake in the heart? To answer these questions, I fed wildtype mice and mice with reduced cardiac fatty acid uptake a diet enriched in n-3s or control diets. Following 10 weeks on diet the mice were subjected to echocardiography to assess if increased fatty acid uptake from an n-3 diet compromises heart function. In addition, both insulin and glucose tolerance was measured to determine whether increased fatty acid uptake contributes to the metabolic changes following an n-3 diet. Furthermore, to investigate which pathways may be involved in fatty acid uptake following an n-3 enriched diet, RNA-sequencing was carried out on mouse hearts fed an n-3 enriched diet or control diets. Analysis of the RNA-seq data suggests that n-3s may be working through peroxisomal proliferator-activated receptor alpha (PPARa) to mediate the increase in fatty acid uptake.

Regulation and Impact of Cardiac Fatty Acid Uptake in Response to n-3 Fatty Acids (Abstract ID: 270971)

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