Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling

Abstract

Rationale: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium.Objective: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. phox from the cytosol to the membranes. Induction of O 2 − production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ-mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ-mediated upregulation of ADIPOQ in EpAT. Methods and Results: Conclusions:We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress. (Circ Res. 2016;118:842-855.

Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria

“…Moreover, rapid atrial beating in pigs and permanent AF in humans are associated with the expression of several genes able to regulate AT accumulation in human and pig atrial myocardium, a phenomenon attributed to an insufficient supply of oxygen and nutriments (11). Another example of cross-talk between AT and the atrial myocardium comes from the observation that human EAT secretes adipokines that regulate the oxidative status of the atrial myocardium (56). EAT expansion also could be caused by nutrient excess in which epicardium becomes engorged with lipids resulting from the overwhelmed capacity of s.c. AT to clear excess triglycerides.…”

Atrial Fibrillation Susceptibility in Obesity

“…1 A recent study using human atrial tissue reported that EAT secreted adipokine influenced myocardial NADPH oxidase activity via endocrine or paracrine effects. 14 Further, this modulation was mutual, in that it was found that oxidation products (such as 4-hydroxynoneal) also regulated the expression of adiponectin in EAT. 14 However the role of other sources of ROS that are important in AF perpetuation e.g., from mitochondria, and how these are related to adipokine production remains to be elucidated.…”

“…14 Further, this modulation was mutual, in that it was found that oxidation products (such as 4-hydroxynoneal) also regulated the expression of adiponectin in EAT. 14 However the role of other sources of ROS that are important in AF perpetuation e.g., from mitochondria, and how these are related to adipokine production remains to be elucidated. It is now well understood that membrane ion channels, as well as intracellular Ca 2+ homeostasis are remodeled in both paroxysmal and persistent AF, and govern both the electrical properties atrial myocytes and fibroblasts, and also cell proliferation in the latter.…”

Prognostic implications of epicardial fat volume quantification in acute pericarditis

“…Recent evidence suggests that epicardial fat affects cardiac biology via the release of adipokines in a paracrine or endocrine manner [7]. Epicardial fat could also have a role in the pathophysiology of acute pericarditis (given its close anatomical affinity with the pericardium), although this hypothesis has never been explored.…”