Abstract 14614: Limited Utilization of Fatty Acid With a Marked Increase in Glucose Uptake Exacerbates Cardiac Dysfunction During Pressure Overload in CD36 Deficient Mice

Background: Fatty acid (FA) is central energy substrate for the heart to generate adenosine triphosphate (ATP) while glucose utilization is dynamically regulated. CD36 is a transmembrane protein which facilitates FA uptake into myocardium. Gene disruption of CD36 in mice (CD36KO) reduced FA uptake by 50% with a 35-fold compensatory increase in glucose uptake in the heart. Purpose: To study whether this metabolic shift from FA to glucose in CD36KO heart is beneficial or detrimental upon pressure overload by transverse aortic constriction (TAC). Methods and Results: Cardiac contraction was significantly reduced in CD36KO-TAC mice with a significant increase in heart weight and fibrosis area compared to wild type (WT)-TAC mice. Glucose uptake, estimated by 18F-FDG, was 5-fold higher in WT-TAC heart compared with WT control while it was 8-fold higher in CD36KO-TAC compared with WT-TAC. FA uptake, estimated by 125I-BMIPP, was declined by 25% in WT-TAC heart while it remained to be reduced in CD36KO-TAC. Metabo...