Regular treadmill exercise inhibits mitochondrial accumulation of cholesterol and oxysterols during myocardial ischemia-reperfusion in wild-type and ob/ob mice.

Abstract

Mitochondria play a central role in the irreversible damages induced to the heart by a prolonged period of ischemia followed by reperfusion. We previously demonstrated that (1) myocardial ischemia-reperfusion induces mitochondrial accumulation of cholesterol and oxysterols that are deleterious for the organelle; (2) inhibition of cholesterol and oxysterol accumulation prevents mitochondrial injury at reperfusion; (3) exercise is cardioprotective and remains efficient in the presence of co-morbidities such as obesity. The aim of this study was to investigate whether regular exercise limits mitochondrial cholesterol and oxysterol accumulation in wild-type and obese mice. Wild-type C57BL/6J and obese (ob/ob) mice were assigned to sedentary conditions or regular treadmill exercise and submitted to 30min of coronary artery occlusion followed by 15min of reperfusion. Regular exercise improved oxidative phosphorylation, restored the antioxidant capacity of the heart by increasing the expression of SOD1 and catalase and reduced the mitochondrial generation of oxysterols in wild-type as well as in ob/ob mice. In wild-type animals, exercise limited the production of oxysterols. In ob/ob mice, despite hypercholesterolemia, chronic exercise abolished the mitochondrial accumulation of cholesterol and concomitantly reduced the generation of 7α-hydroxycholesterol, 7-ketocholesterol and cholesterol-5α,6α-epoxide. In conclusion, regular exercise prevents the mitochondrial accumulation of cholesterol and oxysterols which occurs during early reperfusion of an ischemic myocardium in mice. This effect is observed in normo and hypercholesterolemic animals. It may be partly responsible for the antioxidant properties of regular exercise and contribute to its cardioprotective effect in obese conditions.

• Authors: Julien Musman, Sandrine Pons, Caroline Barau, Claudio Caccia, Valerio Leoni, Alain Berdeaux, Bijan Ghaleh, Didier Morin
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 101 Pg. 317-324 (12 2016) ISSN: 1873-4596 [Electronic] United States
• PMID: 27989751 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Hydroxycholesterols
• Ketocholesterols
• cholesterol alpha-oxide
• cholest-5-en-3 beta,7 alpha-diol
• Cholesterol
• Catalase
• Sod1 protein, mouse
• Superoxide Dismutase-1
• 7-ketocholesterol

Topics

• Animals
• Biological Transport
• Catalase (genetics, metabolism)
• Cholesterol (analogs & derivatives, metabolism)
• Coronary Stenosis (metabolism, pathology, rehabilitation, surgery)
• Gene Expression
• Hydroxycholesterols (metabolism)
• Hypercholesterolemia (metabolism, pathology, prevention & control)
• Ketocholesterols (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Mitochondria, Heart (metabolism, pathology)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Oxidative Phosphorylation
• Physical Conditioning, Animal (physiology)
• Superoxide Dismutase-1 (genetics, metabolism)