Savings precede spending: fatty acid utilization relies on triglyceride formation for cardiac energetics.

Abstract

Fatty acids (FAs) are the primary source for cardiac energy utilization. They account for 70% of myocardial ATP production and glucose; lactate and ketones account for the remaining 30%.1 Earlier studies have suggested that esterified FAs are the major source of cardiac lipids in humans.2 A significant portion of FAs utilized by the heart are derived from dietary fat, whereas the rest are derived from hepatic FAs synthesized from carbohydrates and FAs released after peripheral adipose tissues through lipolysis. Circulating FAs either are esterified to glycerol as a component of lipoprotein triglycerides and phospholipids or circulate as nonesterified free FAs bound to albumin. Palmitic acid (PA) and oleic acid (OA) are the main dietary FAs. Article see p 1790 Free FAs or lipoprotein-derived FAs are taken up primarily by cardiomyocytes via the FA transporter CD36. The fate of FAs after their import into cardiomyocytes has not been fully elucidated. Whether FAs are directly channeled to mitochondria for β oxidation and ATP production or whether storage in intracellular triglycerides and subsequent lipolysis precede FA utilization in mitochondria is a topic of ongoing investigation. Cardiac FA oxidation is centrally regulated by a transcriptional factor of the nuclear receptor family, peroxisome proliferator-activated receptor-α (PPARα). PPARα, similar to the other 2 PPAR isoforms, PPARγ and PPARδ, is activated by FAs and controls the expression of several genes that in …