Copyright © 2007, European Society of Cardiology
Caloric restriction and gender modulate cardiac muscle mitochondrial H2O2 production and oxidative damage
Departament de Biologia Fonamental i Ciències de la Salut, Grup de Metabolisme Energètic i Nutrició, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Palma de Mallorca, Spain
* Corresponding author. Dep. Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Ctra. Valldemossa km 7.5. E-07122, Palma de Mallorca, Spain. Tel.: +34 971 173173; fax: +34 971 173 184. Email address: paco.garcia-palmer{at}uib.es
Objective: Gender and diet have an important effect in cardiovascular disease and other aging-associated disorders, whose initiation and/or worsening seem to be delayed in females from different species and in animals subjected to caloric restriction (CR). The aim of the present study was to investigate whether cardiac muscle bioenergetic mitochondrial features could be responsible for these beneficial effects.
Methods: Fifteen-month-old male and female Wistar rats were fed ad libitum or subjected to 40% CR for 3 months. Cardiac mitochondrial function (citrate synthase activity, oxygen consumption), activity of complexes I, III, IV and ATPase of the OXPHOS system, antioxidant activities (MnSOD, GPx), mitochondrial DNA and protein content, mitochondrial H2O2 production, heart oxidative damage, complex IV and ATPase content and efficiency, as well as protein levels of mitochondrial transcription factor A (TFAM) and peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC1
) were measured.
Results: Female and CR rats exhibited lower cardiac mitochondria content, which were more efficient and generated less H2O2 than in males and ad libitum fed animals, with their consequent lower heart oxidative damage.
Conclusion: Higher mitochondrial differentiation becomes a metabolic adaptation to increase energy efficiency, as what happens in female and CR rats. This adaptation is associated with their lower mitochondrial free radical production and oxidative damage, which could help to understand the mechanism by which these animals exhibit a lower incidence of aging-related disorders, including cardiovascular disease.
KEYWORDS Energy metabolism; Gender; Mitochondria; Oxidative phosphorylation; Oxygen radicals