Abstract
The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload. CD36KO mice exhibited contractile dysfunction and death from heart failure with enhanced cardiac hypertrophy and interstitial fibrosis when they were subjected to transverse aortic constriction (TAC). The pool size in the TCA cycle and levels of high-energy phosphate were significantly reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts, which could cause a further decline of the pool size. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overload-induced hypertrophy.
Highlights
The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization
Six out of 18 CD36 knockout (CD36KO)-transverse aortic constriction (TAC) mice died by 8 weeks after TAC, but no mice died in WT-TAC
Echocardiographic analysis revealed that while no functional difference between CD36KO and WT mice was observed at baseline, diminished % fractional shortening and increased LV diastolic and systolic chamber diameter was more prominent in CD36KO-TAC mice all measured time points after 1 week (Fig. 1B and Table S1)
Summary
The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overloadinduced hypertrophy. It was recently reported that cardiomyocyte-specific deletion of CD36 accelerates cardiac contractile dysfunction in response to pressure overload Feeding these CD36KO mice a diet enriched in medium-chain fat, which bypasses CD36 for entry into the cardiomyocyte, is able to protect these mice from developing heart failure[13]. Cardiac metabolism (catabolism and anabolism) and energetic status under pressure overload in vivo remains unanswered
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
