The PPAR𝛼-PGC-1𝛼 Axis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium

Figure 2

Dynamic regulation of PPAR𝛼-PGC-1𝛼 complex activity in developing, failing, and diabetic heart. Physiological cardiac growth resulting from postnatal maturation is associated with increased PPAR𝛼 and PGC-1𝛼 expression and marked expansion of mitochondrial volume density and oxidative capacity. Conversely, pathologic hypertrophy is linked to decreased PPAR𝛼-PGC-1𝛼 expression and/or activity and diminished reliance on oxidative mitochondrial metabolism often leading to intramyocellular lipid accumulation. Finally, in the diabetic heart, PPAR𝛼-PGC-1𝛼 complex activity is increased along with the cardiac reliance on FAO. Despite of high-level FAO, the cardiac lipid accumulation is a hallmark of the diabetic heart and lipotoxicity may play a key role in the development of diabetic cardiomyopathy.