A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart.
Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed ra...
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Springer Medizin
2011
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my.iium.irep.189262013-06-20T04:41:56Z http://irep.iium.edu.my/18926/ A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart. M.A, Cole A.J, Murray L.E, Cochlin L.C, Heather S., McAleese N.S, Knight E., Sutton Abd. Jamil, Amira Hajirah N., Parassol K., Clarke Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed rats a high fat diet (55% kcal from fat) or standard laboratory chow (7% kcal from fat) for 3 weeks, after which we measured cardiac function in vivo using cine MRI, efficiency in isolated working hearts and respiration rates and ADP/O ratios in isolated interfibrillar mitochondria; also, measured were medium chain acyl-CoA dehydrogenase (MCAD) and citrate synthase activities plus uncoupling protein 3 (UCP3), mitochondrial thioesterase 1 (MTE-1), adenine nucleotide translocase (ANT) and ATP synthase protein levels. We found that in vivo cardiac function was the same for all rats, yet oxygen consumption was 19% higher in high fatfed rat hearts, therefore, efficiency was 21% lower than in controls. We found that mitochondrial fatty acid oxidation rates were 25% higher, and MCAD activity was 23% higher, in hearts from rats fed the high fat diet when compared with controls. Mitochondria from high fat-fed rat hearts had lower ADP/O ratios than controls, indicating increased respiratory uncoupling, which was ameliorated by GDP, a UCP3 inhibitor. Mitochondrial UCP3 and MTE- 1 levels were both increased by 20% in high fat-fed rat hearts when compared with controls, with no significant change in ATP synthase or ANT levels, or citrate synthase activity. We conclude that increased cardiac oxygen utilisation, and thereby decreased cardiac efficiency, occurs in non-genetic obesity, which is associated with increased mitochondrial uncoupling due to elevated UCP3 and MTE-1 levels. Keywords Cardiac efficiency � Oxygen consumption � Free fatty acids � Uncoupling � High fat diet � Mitochondria Springer Medizin 2011-05 Article REM application/pdf en http://irep.iium.edu.my/18926/1/A-high-fat-diet-increases-mitochondrial-fatty-acid-oxidation-and-uncoupling-to-decrease-efficiency-in-rat-heart_2011_Basic-Research-in-Cardiology.pdf M.A, Cole and A.J, Murray and L.E, Cochlin and L.C, Heather and S., McAleese and N.S, Knight and E., Sutton and Abd. Jamil, Amira Hajirah and N., Parassol and K., Clarke (2011) A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart. Basic Research in Cardiology, 106 (3). pp. 447-457. ISSN 0300-8428 http:/Springerlink.com 10.1007/s00395-011-0156-1 |
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| description |
Elevated levels of cardiac mitochondrial
uncoupling protein 3 (UCP3) and decreased cardiac
efficiency (hydraulic power/oxygen consumption) with
abnormal cardiac function occur in obese, diabetic mice.
To determine whether cardiac mitochondrial uncoupling
occurs in non-genetic obesity, we fed rats a high fat diet
(55% kcal from fat) or standard laboratory chow (7% kcal
from fat) for 3 weeks, after which we measured cardiac
function in vivo using cine MRI, efficiency in isolated
working hearts and respiration rates and ADP/O ratios in
isolated interfibrillar mitochondria; also, measured were
medium chain acyl-CoA dehydrogenase (MCAD) and citrate
synthase activities plus uncoupling protein 3 (UCP3),
mitochondrial thioesterase 1 (MTE-1), adenine nucleotide
translocase (ANT) and ATP synthase protein levels. We
found that in vivo cardiac function was the same for all
rats, yet oxygen consumption was 19% higher in high fatfed
rat hearts, therefore, efficiency was 21% lower than in
controls. We found that mitochondrial fatty acid oxidation
rates were 25% higher, and MCAD activity was 23%
higher, in hearts from rats fed the high fat diet when
compared with controls. Mitochondria from high fat-fed rat
hearts had lower ADP/O ratios than controls, indicating
increased respiratory uncoupling, which was ameliorated
by GDP, a UCP3 inhibitor. Mitochondrial UCP3 and MTE-
1 levels were both increased by 20% in high fat-fed rat
hearts when compared with controls, with no significant
change in ATP synthase or ANT levels, or citrate synthase
activity. We conclude that increased cardiac oxygen utilisation, and thereby decreased cardiac efficiency, occurs in non-genetic obesity, which is associated with increased mitochondrial uncoupling due to elevated UCP3 and
MTE-1 levels.
Keywords Cardiac efficiency � Oxygen consumption �
Free fatty acids � Uncoupling � High fat diet � Mitochondria |
| format |
Article |
| author |
M.A, Cole A.J, Murray L.E, Cochlin L.C, Heather S., McAleese N.S, Knight E., Sutton Abd. Jamil, Amira Hajirah N., Parassol K., Clarke |
| spellingShingle |
M.A, Cole A.J, Murray L.E, Cochlin L.C, Heather S., McAleese N.S, Knight E., Sutton Abd. Jamil, Amira Hajirah N., Parassol K., Clarke A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart. |
| author_facet |
M.A, Cole A.J, Murray L.E, Cochlin L.C, Heather S., McAleese N.S, Knight E., Sutton Abd. Jamil, Amira Hajirah N., Parassol K., Clarke |
| author_sort |
M.A, Cole |
| title |
A high fat diet increases mitochondrial fatty acid oxidation
and uncoupling to decrease efficiency in rat heart. |
| title_short |
A high fat diet increases mitochondrial fatty acid oxidation
and uncoupling to decrease efficiency in rat heart. |
| title_full |
A high fat diet increases mitochondrial fatty acid oxidation
and uncoupling to decrease efficiency in rat heart. |
| title_fullStr |
A high fat diet increases mitochondrial fatty acid oxidation
and uncoupling to decrease efficiency in rat heart. |
| title_full_unstemmed |
A high fat diet increases mitochondrial fatty acid oxidation
and uncoupling to decrease efficiency in rat heart. |
| title_sort |
high fat diet increases mitochondrial fatty acid oxidation
and uncoupling to decrease efficiency in rat heart. |
| publisher |
Springer Medizin |
| publishDate |
2011 |
| url |
http://irep.iium.edu.my/18926/1/A-high-fat-diet-increases-mitochondrial-fatty-acid-oxidation-and-uncoupling-to-decrease-efficiency-in-rat-heart_2011_Basic-Research-in-Cardiology.pdf http://irep.iium.edu.my/18926/ http:/Springerlink.com |
| _version_ |
1643607552692322304 |
| score |
13.211869 |