Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function

ABSTRACT: Changes in the acetylation status of mitochondrial proteins have been linked to the development of metabolic dysfunction in a number of tissues. Increased lysine acetylation has been reported in the hearts of obese mice, and is associated with changes in fuel metabolism, redox status, and mitochondrial oxidative phosphorylation. In this study, we examined whether diet-induced changes in the acetylation of mitochondrial acyl-CoA dehydrogenases affected fatty acid oxidation enzyme activity and contractile function in the obese mouse heart. Exposure to a long-term high fat diet in wildtype mice led to the hyperacetylation of short- and long-chain acyl-CoA dehydrogenases SCAD and LCAD, which correlated with their increased enzymatic activity in vitro. Cardiomyocyte-specific deletion of the mitochondrial acetyltransferase-related protein GCN5L1 prevented both the hyperacetylation and increased activity of these enzymes under the same conditions of dietary excess. Despite the potential for increased cardiac fatty acid oxidation activity, wildtype mice did not display any increase in cardiac contractility following exposure to a high fat diet. We conclude that the potential energetic benefits of elevated fatty acid oxidation activity are not sufficient to counter the various deleterious effects of a high fat diet on cardiac function. Graphical abstract Image 1 Highlights • Exposure to a high fat diet increases the levels of lysine acetylation detected on cardiac fatty acid oxidation enzymes.• Hyperacetylated fatty acid oxidation enzymes in the heart display increased rates of activity in vitro.• Increased acetylation in high fat diet-exposed hearts is dependent on the mitochondrial acetyltransferase protein GCN5L1.• In vitro fatty acid oxidation enzyme activity does not correlate with cardiac contractile function in high fat diet fed mice.

SUBMITTER: Thapa D 

PROVIDER: S-EPMC8562190 | biostudies-literature |

REPOSITORIES: biostudies-literature