Requirement of Fatty Acid Oxidation to Attenuate Cardiac Hypertrophy

Heart enlargement, or cardiac hypertrophy, is an increasingly prevalent condition in the obese, aging, diabetic, and hypertensive populations. It is characterized by reductions in mitochondrial fatty acid oxidation, yet the role fatty acid oxidation plays in cardiac remodeling remains unclear. We have previously demonstrated that the loss of mouse cardiac carnitine palmitoyltransferase 2 (Cpt2 M−/− ), an enzyme required for mitochondrial long‐chain fatty acid oxidation, causes cardiac hypertrophic remodeling and early lethality. Cpt2 M−/− mice are resistant to two therapies previously shown to attenuate hypertrophy: inhibition of mTOR and reversal of protein hypoacetylation, suggesting that improving mitochondrial fatty acid oxidation is key for attenuating cardiac hypertrophy. To determine if restoring mitochondrial oxidative flux with alternative substrates to long‐chain fatty acids could improve hypertrophy, control and Cpt2 M−/− mice were placed on either control diet or specialized ketogenic diet enriched with octanoate, a medium‐chain fatty acid that can bypass CPT2 for mitochondrial oxidation. While ketogenic diets have been shown to improve cardiac hypertrophy, we report here that in the absence of CPT2, ketogenic octanoate‐enriched diet failed to improve hypertrophy. We will further describe the molecular and metabolic consequences of the ketogenic octanoate‐enriched diet on the heart with and without CPT2. Determining the molecular events that fail to be modified in the Cpt2 M−/− heart in response to this therapy will elucidate pathways that link fatty acid oxidation to cardiac remodeling. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .