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Mouse Carnitine Palmitoyltransferase 2 (CPT2) is required to sustain cardiac function
Author(s) -
Ellis Jessica M,
Hasek Like Y,
Yurovich Elizaveta J,
Harris Kate L,
Goergen Craig J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.684.8
Subject(s) - beta oxidation , carnitine o palmitoyltransferase , endocrinology , medicine , carnitine , cardiac function curve , malonyl coa , chemistry , heart failure , metabolism
Carnitine palmitoyltransferase 2 (CPT2) is an enzyme required for the acyl‐carnitine shuttle that controls mitochondrial long‐chain fatty acid oxidation. The role of CPT2 in fatty acid metabolism is well established. However, patients with early‐onset CPT2 deficiency suffer cardiac complications and it has remained unknown how the loss of CPT2 in the heart alters cardiac function due to the lack of a physiological model. Here we present a novel mouse model deficient in cardiac CPT2 ( Cpt2 M−/− ) which causes severe cardiac hypertrophy and eventual cardiac failure. Cpt2 M−/− hearts weigh up to 4‐fold that of control hearts within 8–12 weeks of age and the mice fail to survive beyond 15 weeks of age. The Cpt2 M−/− mice maintain a normal body weight and adiposity during their short lifespan. The loss of cardiac CPT2 reduced long‐chain fatty acid oxidation in heart homogenates by 93%. The loss of cardiac CPT2 increases the abundance of mitochondrial proteins, protein acetylation, activation of the mTOR pathway, and reduces insulin‐stimulated induction of the insulin‐signaling pathway. Together, these data suggest that CPT2‐mediated flux of fatty acid oxidation is required to retain insulin sensitivity and to sustain cardiac function.