Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function
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 mitochondr...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Current Research in Physiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665944120300122 |
| _version_ | 1818381819887747072 |
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| author | Dharendra Thapa Janet R. Manning Bellina A.S. Mushala Michael W. Stoner Manling Zhang Iain Scott |
| author_facet | Dharendra Thapa Janet R. Manning Bellina A.S. Mushala Michael W. Stoner Manling Zhang Iain Scott |
| author_sort | Dharendra Thapa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T02:40:39Z |
| format | Article |
| id | doaj.art-5d2ade7a4107401eb029ae9653621c09 |
| institution | Directory Open Access Journal |
| issn | 2665-9441 |
| language | English |
| last_indexed | 2024-12-14T02:40:39Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Physiology |
| spelling | doaj.art-5d2ade7a4107401eb029ae9653621c092022-12-21T23:20:01ZengElsevierCurrent Research in Physiology2665-94412020-12-0134449Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile functionDharendra Thapa0Janet R. Manning1Bellina A.S. Mushala2Michael W. Stoner3Manling Zhang4Iain Scott5Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USAVascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USAVascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USAVascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USAVascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USAVascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Corresponding author. Division of Cardiology, University of Pittsburgh, BST E1259, 200 Lothrop Street, Pittsburgh, PA, 15261, USA.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.http://www.sciencedirect.com/science/article/pii/S2665944120300122GCN5L1MitochondriaLysine acetylationFatty acid oxidationCardiac contractility |
| spellingShingle | Dharendra Thapa Janet R. Manning Bellina A.S. Mushala Michael W. Stoner Manling Zhang Iain Scott Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function Current Research in Physiology GCN5L1 Mitochondria Lysine acetylation Fatty acid oxidation Cardiac contractility |
| title | Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function |
| title_full | Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function |
| title_fullStr | Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function |
| title_full_unstemmed | Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function |
| title_short | Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function |
| title_sort | increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function |
| topic | GCN5L1 Mitochondria Lysine acetylation Fatty acid oxidation Cardiac contractility |
| url | http://www.sciencedirect.com/science/article/pii/S2665944120300122 |
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