Influence of diet-induced obesity and voluntary exercise training on cardiac lipids and mitochondrial function in mice.

BACKGROUND

Obesity is a risk factor for developing cardiometabolic disease. Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality. This study examined the effect of high-fat feeding on cardiac morphology and mitochondrial function, alongside the mitigating effects of voluntary exercise training.

METHODS

Six-week-old male C57Bl/6 J mice commenced a high fat diet (HFD) or chow diet and were randomized to receive locked (sedentary) or unlocked (voluntary exercise training (VET)) running wheels at 10 weeks of age. Mice were monitored until 30 weeks of age and euthanized for collection of tissues. Magnetic resonance imaging was performed to assess body composition, and echocardiography was performed to assess cardiac function.

RESULTS

Compared with chow-fed animals, the HFD increased body weight and adiposity and decreased cardiolipins (CL) in the heart, which are required for maintaining adequate mitochondrial respiration. Importantly, VET reversed these effects and induced physiological cardiac hypertrophy. Cardiac mitochondrial respiratory chain analysis revealed decreased complexes II and IV activity following high fat feeding, while VET enhanced complex I activity, emphasizing the cardioprotective effect of exercise training in obesity.

CONCLUSION

This study uncovers mechanisms by which obesity and exercise impact cardiac mitochondrial health and suggests the mitochondria is a therapeutic target in obesity-related cardiovascular diseases.