Abstract
Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob/ob mice), when treated orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week of life). We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE), a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.
Highlights
Adult obesity is a worldwide pandemic condition that leads to the metabolic syndrome and a spectrum of irreversible cardiovascular, neurological, renal and digestive morbidities [1,2].cardiovascular diseases still represent the leading cause of death in obesity linked to hypertension, diastolic dysfunction and hypercoagulability [3,4]
The aim of the present study was to assess the effect of oral supplementation of melatonin on cardiomyocytes, mainly on mitochondria and pericardial fat in pre-diabetic leptin-deficient ob/ob mice
At heart level, the complex mitochondrial alterations that occur during obesity and, remarkably, we suggested that melatonin might be a safe preventive dietary adjuvant able to impair cardiac hypoxic status in pre-diabetic leptin-deficient mice
Summary
Adult obesity is a worldwide pandemic condition that leads to the metabolic syndrome and a spectrum of irreversible cardiovascular, neurological, renal and digestive morbidities [1,2]. Cardiovascular diseases still represent the leading cause of death in obesity linked to hypertension, diastolic dysfunction and hypercoagulability [3,4]. Recent studies aimed to discover the pathogenesis of heart failure have underlined the crucial involvement of mitochondria dysfunctions that may precede the myocardial damage [5,6]. The therapeutic role of drugs able to target mitochondria dysfunctions is an intriguing and promising field of cardiovascular research [7,8]. To best address combined cellular events that concur in obesity, diabetes and related-cardiovascular dysfunctions, rodent models are still the best choice [9]. To adopt an experimental in vivo approach to mimic human obesity there are two main different translational
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
