Abstract 17595: Characterization of Cardiac Lipotoxic Stress

Introduction: Accumulation of lipids in the heart, or cardiac steatosis, has been demonstrated in both insulin resistant and diabetic patients and is associated with diastolic dysfunction. However, the pathological mechanisms causing this cardiac lipotoxicity have yet to be fully elucidated. High fat diets have been shown to induce endoplasmic reticulum (ER) stress in a variety of tissues including liver, skeletal muscle and brain. Here we were interested in characterizing the ER stress response in primary cardiomyocytes treated with lipids as well as hearts from high fat fed mice. Methods and Results: We evaluated ER stress in mouse neonatal cardiomyocytes (mNCMs) treated with either saturated (palmitate) or mono-unsaturated (oleate) fatty acids, as well as in cardiac tissue from C57bl/6 mice fed a high fat diet. We evaluated the expression of Atf-4 & -6, Grp78, spliced Xbp1, Dnajb9, and Herp mRNA levels as well as protein levels of Atf6, Grp78 and phosphorylated Perk. We demonstrated significant inducti...