On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury
The role of peroxisome proliferator activated alpha (PPARα) -mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 weeks before in vivo contractile function was measured using cine magnetic resonance (MR) imaging. In isolated,...
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| Format: | Article |
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Federation of American Society of Experimental Biology
2016
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| Online Access: | https://eprints.nottingham.ac.uk/34100/ |
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| author | Cole, Mark Abd Jamil, Amira H. Heather, Lisa C. Murray, Andrew J. Sutton, Elizabeth R. Slingo, Mary Sebag-Montefiore, Liam Tan, Suat Cheng Aksentijević, Dunja Gildea, Ottilie S. Stuckey, Daniel J. Yeoh, Kar Kheng Carr, Carolyn A. Evans, Rhys D. Aasum, Ellen Schofield, Christopher J. Ratcliffe, Peter J. Neubauer, Stefan Robbins, Peter A. Clarke, Kieran |
| author_facet | Cole, Mark Abd Jamil, Amira H. Heather, Lisa C. Murray, Andrew J. Sutton, Elizabeth R. Slingo, Mary Sebag-Montefiore, Liam Tan, Suat Cheng Aksentijević, Dunja Gildea, Ottilie S. Stuckey, Daniel J. Yeoh, Kar Kheng Carr, Carolyn A. Evans, Rhys D. Aasum, Ellen Schofield, Christopher J. Ratcliffe, Peter J. Neubauer, Stefan Robbins, Peter A. Clarke, Kieran |
| author_sort | Cole, Mark |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The role of peroxisome proliferator activated alpha (PPARα) -mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 weeks before in vivo contractile function was measured using cine magnetic resonance (MR) imaging. In isolated, perfused hearts, energetics were measured using 31P MR spectroscopy and glycolysis and fatty acid oxidation were measured using 3H labelling. Compared with normoxic, chow-fed control mouse heart, hypoxia decreased PPARα expression, fatty acid oxidation and mitochondrial UCP3 levels, while increasing glycolysis, all of which served to maintain normal ATP concentrations and thereby ejection fractions. A high-fat diet increased cardiac PPARα expression, fatty acid oxidation and UCP3 levels, with decreased glycolysis. Hypoxia was unable to alter the high PPARα expression or reverse the metabolic changes caused by the high fat diet, with the result that ATP concentrations and contractile function decreased significantly. The adaptive metabolic changes caused by hypoxia in control mouse hearts were found to have already occurred in PPARα-/- mouse hearts, and sustained function in hypoxia despite an inability for further metabolic remodelling. We conclude that decreased cardiac PPARα expression is essential for adaptive metabolic remodelling in hypoxia, but is prevented by dietary fat. |
| first_indexed | 2025-11-14T19:21:32Z |
| format | Article |
| id | nottingham-34100 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:21:32Z |
| publishDate | 2016 |
| publisher | Federation of American Society of Experimental Biology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-341002020-05-04T17:58:12Z https://eprints.nottingham.ac.uk/34100/ On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury Cole, Mark Abd Jamil, Amira H. Heather, Lisa C. Murray, Andrew J. Sutton, Elizabeth R. Slingo, Mary Sebag-Montefiore, Liam Tan, Suat Cheng Aksentijević, Dunja Gildea, Ottilie S. Stuckey, Daniel J. Yeoh, Kar Kheng Carr, Carolyn A. Evans, Rhys D. Aasum, Ellen Schofield, Christopher J. Ratcliffe, Peter J. Neubauer, Stefan Robbins, Peter A. Clarke, Kieran The role of peroxisome proliferator activated alpha (PPARα) -mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 weeks before in vivo contractile function was measured using cine magnetic resonance (MR) imaging. In isolated, perfused hearts, energetics were measured using 31P MR spectroscopy and glycolysis and fatty acid oxidation were measured using 3H labelling. Compared with normoxic, chow-fed control mouse heart, hypoxia decreased PPARα expression, fatty acid oxidation and mitochondrial UCP3 levels, while increasing glycolysis, all of which served to maintain normal ATP concentrations and thereby ejection fractions. A high-fat diet increased cardiac PPARα expression, fatty acid oxidation and UCP3 levels, with decreased glycolysis. Hypoxia was unable to alter the high PPARα expression or reverse the metabolic changes caused by the high fat diet, with the result that ATP concentrations and contractile function decreased significantly. The adaptive metabolic changes caused by hypoxia in control mouse hearts were found to have already occurred in PPARα-/- mouse hearts, and sustained function in hypoxia despite an inability for further metabolic remodelling. We conclude that decreased cardiac PPARα expression is essential for adaptive metabolic remodelling in hypoxia, but is prevented by dietary fat. Federation of American Society of Experimental Biology 2016-08-01 Article PeerReviewed Cole, Mark, Abd Jamil, Amira H., Heather, Lisa C., Murray, Andrew J., Sutton, Elizabeth R., Slingo, Mary, Sebag-Montefiore, Liam, Tan, Suat Cheng, Aksentijević, Dunja, Gildea, Ottilie S., Stuckey, Daniel J., Yeoh, Kar Kheng, Carr, Carolyn A., Evans, Rhys D., Aasum, Ellen, Schofield, Christopher J., Ratcliffe, Peter J., Neubauer, Stefan, Robbins, Peter A. and Clarke, Kieran (2016) On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury. FASEB Journal, 30 (8). pp. 2684-2697. ISSN 0892-6638 Cardiac contractile function; Cine magnetic resonance imaging; Hypoxia inducible factor (HIF); Myocardial energy metabolism; 31 P Magnetic resonance spectroscopy; Substrate metabolism http://www.fasebj.org/content/30/8/2684 doi:10.1096/fj.201500094R doi:10.1096/fj.201500094R |
| spellingShingle | Cardiac contractile function; Cine magnetic resonance imaging; Hypoxia inducible factor (HIF); Myocardial energy metabolism; 31 P Magnetic resonance spectroscopy; Substrate metabolism Cole, Mark Abd Jamil, Amira H. Heather, Lisa C. Murray, Andrew J. Sutton, Elizabeth R. Slingo, Mary Sebag-Montefiore, Liam Tan, Suat Cheng Aksentijević, Dunja Gildea, Ottilie S. Stuckey, Daniel J. Yeoh, Kar Kheng Carr, Carolyn A. Evans, Rhys D. Aasum, Ellen Schofield, Christopher J. Ratcliffe, Peter J. Neubauer, Stefan Robbins, Peter A. Clarke, Kieran On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| title | On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| title_full | On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| title_fullStr | On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| title_full_unstemmed | On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| title_short | On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| title_sort | on the pivotal role of ppara in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury |
| topic | Cardiac contractile function; Cine magnetic resonance imaging; Hypoxia inducible factor (HIF); Myocardial energy metabolism; 31 P Magnetic resonance spectroscopy; Substrate metabolism |
| url | https://eprints.nottingham.ac.uk/34100/ https://eprints.nottingham.ac.uk/34100/ https://eprints.nottingham.ac.uk/34100/ |