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The role of fatty acid oxidation in cardiac remodeling and acylation
Author(s) -
Ellis Jessica
Publication year - 2017
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.31.1_supplement.276.2
Subject(s) - endocrinology , medicine , beta oxidation , carnitine , lipotoxicity , mitochondrion , carnitine o palmitoyltransferase , muscle hypertrophy , biology , fatty acid metabolism , diabetes mellitus , metabolism , insulin resistance , biochemistry
Cardiac mitochondrial metabolism has emerged as a major mediator of cell function and cardiac hypertrophic remodeling, a phenomenon observed in an array of conditions including obesity, diabetes, and hypertension. However, the metabolic and mechanistic drivers of hypertrophy remain elusive. Mitochondrial long‐chain fatty acid oxidation requires carnitine palmitoyltransferase 2 (CPT2) an obligate enzyme of the acyl‐carnitine shuttle. We have generated mice with heart and skeletal muscle‐specific‐CPT2 deficiency (Cpt2 M−/− ). The loss of heart and muscle CPT2 does not alter whole body energetics and adiposity; however, the Cpt2 M−/− mice develop cardiac hypertrophy, dysregulated mitochondrial function, and early lethality. CPT2 deficient hearts do not develop fibrosis and are resistant to rapamycin‐induced alleviation of hypertrophic remodeling. Intriguingly, the hypertrophy occurs in the setting of 50% reduced lysine acetylation across subcellular compartments. Protein acetylation is regulated by fluctuations in mitochondrial metabolism and is a potential mediator of cardiac hypertrophic remodeling. We are exploring the role of protein acetylation in CPT2‐deficiency‐induced cardiac remodeling and mitochondrial function.