Abstract 4139747: Inhibition of Acetyl -CoA Carboxylase 2 (ACC2) enhances fatty acid oxidation and improves cardiac function and survival in a severe model of heart failure

Authors: Mai Usui, Yu Tsurekawa, Tatsuya Ikehara, Atsuyuki Shimazaki, Archana Vijayakumar, Robert Myers, G. Mani Subramanian, Eisuke Murakami

Published: 2024-11-14

DOI: 10.1161/circ.150.suppl_1.4139747

Source: Full article

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Abstract

Heart failure (HF) is characterized by disordered energy metabolism including impaired mitochondrial oxidation and altered energy substrate preference. In triglyceride (TG) deposit cardiomyovasculopathy (TGCV; ORPHA code 565612), a rare form of HF characterized by impaired fatty acid oxidation (FAO), massive TG accumulation occurs in cardiac muscle and vasculature due to deficiency of adipose triglyceride lipase (ATGL). Since acetyl-CoA carboxylase 2 (ACC2) regulates fatty acid transport into mitochondria for oxidation, we hypothesized that genetic deletion or pharmacologic inhibition of ACC2 may improve cardiac function in the