The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical and experimental evidence supports the existence of a unique disease entity termed "obesity cardiomyopathy", which develops independent of hypertension, coronary heart disease and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically-predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy.

Biological aging is an inevitable and independent risk factor for a wide array of chronic diseases including cardiovascular and metabolic diseases. Ample evidence has established a pivotal role for interrupted mitochondrial homeostasis in the onset and development of aging-related cardiovascular anomalies. A number of culprit factors have been suggested in aging-associated mitochondrial anomalies including oxidative stress, lipid toxicity, telomere shortening, metabolic disturbance, and DNA damage, with recent findings revealing a likely role for compromised mitochondrial dynamics and mitochondrial quality control machinery such as autophagy. Mitochondria undergo consistent fusion and fission, which are crucial for mitochondrial homeostasis and energy adaptation. Autophagy, in particular, mitochondria-selective autophagy, namely, mitophagy, refers to a highly conservative cellular process to degrade and clear long-lived or damaged cellular organelles including mitochondria, the function of which gradually deteriorates with increased age. Mitochondrial homeostasis could be achieved through a cascade of independent but closely related processes including fusion, fission, mitophagy, and mitochondrial biogenesis. With improved health care and increased human longevity, the ever-rising aging society has imposed a high cardiovascular disease prevalence. It is thus imperative to understand the role of mitochondrial homeostasis in the regulation of lifespan and healthspan. Targeting mitochondrial homeostasis should offer promising novel therapeutic strategies against aging-related complications, particularly cardiovascular diseases.