Cardiolipin Alterations during Obesity: Exploring Therapeutic Opportunities

SIMPLE SUMMARY: Understanding the deleterious mechanisms of obesity and ultimately reversing them requires the identification of the key players of metabolic homeostasis altered in this condition. Cardiolipin appears to be one of these. This phospholipid is specifically enriched in mitochondria, the energy powerhouse of cells that converts energy substrates into ATP, the universal energy form of cellular metabolism. Due to its particular structure, cardiolipin confers unique properties to mitochondria and plays a central role in energy production. In this review, we gather a large body of evidence showing the impact of obesity on the quantity and quality of cardiolipin which likely participates in the progressive mitochondrial failure accompanying obesity. However, we also show that different approaches to correct these alterations can improve cellular metabolism and mitigate the consequences of obesity. Furthermore, we report that modulation of cardiolipin could serve as a lever to temporarily increase mitochondrial energy expenditure and induce weight loss. Beyond its deleterious alterations during obesity, cardiolipin could thus offer opportunities in the fight against obesity. ABSTRACT: Cardiolipin is a specific phospholipid of the mitochondrial inner membrane that participates in many aspects of its organization and function, hence promoting proper mitochondrial ATP production. Here, we review recent data that have investigated alterations of cardiolipin in different tissues in the context of obesity and the related metabolic syndrome. Data relating perturbations of cardiolipin content or composition are accumulating and suggest their involvement in mitochondrial dysfunction in tissues from obese patients. Conversely, cardiolipin modulation is a promising field of investigation in a search for strategies for obesity management. Several ways to restore cardiolipin content, composition or integrity are emerging and may contribute to the improvement of mitochondrial function in tissues facing excessive fat storage. Inversely, reduction of mitochondrial efficiency in a controlled way may increase energy expenditure and help fight against obesity and in this perspective, several options aim at targeting cardiolipin to achieve a mild reduction of mitochondrial coupling. Far from being just a victim of the deleterious consequences of obesity, cardiolipin may ultimately prove to be a possible weapon to fight against obesity in the future.