The role of oxidative stress in the crosstalk between leptin and mineralocorticoid receptor in the cardiac fibrosis associated with obesity

Abstract

We have investigated whether mineralocorticoid receptor activation can participate in the profibrotic effects of leptin in cardiac myofibroblasts, as well as the potential mechanisms involved. The presence of eplerenone reduced the leptin-induced increase in protein levels of collagen I, transforming growth factor β, connective tissue growth factor and galectin-3 and the levels of both total and mitochondrial of superoxide anion (O2 . −) in cardiac myofibroblasts. Likewise, the MEK/ERK inhibitor, PD98059, and the PI3/Akt inhibitor, LY294002, showed a similar pattern. Mitochondrial reactive oxygen species (ROS) scavenger (MitoTempo) attenuated the increase in body weight observed in rats fed a high fat diet (HFD). No differences were found in cardiac function or blood pressure among any group. However, the cardiac fibrosis and enhanced O2 .-levels observed in HFD rats were attenuated by MitoTempo, which also prevented the increased circulating leptin and aldosterone levels in HFD fed animals. This study supports a role of mineralocorticoid receptor in the cardiac fibrosis induced by leptin in the context of obesity and highlights the role of the mitochondrial ROS in this process.

The Crosstalk between Cardiac Lipotoxicity and Mitochondrial Oxidative Stress in the Cardiac Alterations in Diet-Induced Obesity in Rats

“…An exacerbation of oxidative stress, mainly from mitochondrial origin, is linked to mitochondrial lipid remodeling and, in consequence, the cardiac damage associated with obesity, since the administration of MitoQ was able to normalize the cardiolipotoxicity, mitochondrial alterations and the cardiac consequences of obesity. A role of oxidative stress has also been reported in the cardiac damage associated, not only with obesity, but also with aging, heart failure and hypertension [10,51,52]. In this regard, myocardial ischemia-reperfusion was accompanied by changes in cardiac metabolism in a model of non-obese and non-diabetic mice with ectopic lipid deposition, leading to severe myocardial dysfunction.…”

“…Mitochondria comprise almost a third of cardiomyocyte volume, are the source of ATP, and play a central role in the calcium homeostasis necessary for maintaining cardiomyocyte viability and contractility. Mitochondria are also the main source of reactive oxygen species (ROS), which can be exacerbated in different pathological conditions, including obesity [10,11]. Dysregulation of mitochondrial function in the context of obesity can participate not only in the cardiac consequences of obesity, but as well as in its metabolic ones, since the administration of a mitochondrial antioxidant was able to improve cardiac damage and improve insulin resistance in adipose tissue associated with obesity [10,[12][13][14].…”

“…Mitochondria are also the main source of reactive oxygen species (ROS), which can be exacerbated in different pathological conditions, including obesity [10,11]. Dysregulation of mitochondrial function in the context of obesity can participate not only in the cardiac consequences of obesity, but as well as in its metabolic ones, since the administration of a mitochondrial antioxidant was able to improve cardiac damage and improve insulin resistance in adipose tissue associated with obesity [10,[12][13][14]. Although the potential role of cardiolipotoxicity and mitochondrial oxidative stress in the cardiac damage associated with obesity is accepted, how these two mechanisms interact in this damage remains unclear.…”

A mitochondria-targeted antioxidant and a thyroid hormone affect carotenoid ketolase gene expression and bill redness in zebra finches

“…It contradicts studies where rodents fed with a high caloric diet did not gain mass when treated with this compound (Jeong et al . 2016; Gutiérrez-Tenorio et al . 2017).…”

Derangements in adrenergic–adipokine signalling establish a neurohormonal basis for obesity‐related heart failure with a preserved ejection fraction

“…Leptin promotes sodium retention by stimulating the renin–angiotensin system, the renal sympathetic nerves and aldosterone secretion from the adrenal gland . Additionally, leptin promotes inflammation and fibrosis of the neighbouring myocardium (in concert with enhanced mineralocorticoid receptor signalling); this process not only affects the ventricles, but also the atria, thus predisposing to atrial fibrillation—a common cardiac arrhythmia in patients with HFpEF. Fibrosis may also affect the pericardium, further limiting ventricular distensibility .…”