Heart-adipose tissue cross-talk

Recent evidence suggests that adipose tissue (AT) affects vascular and cardiac function through the release of bioactive molecules called adipokines. Adiponectin, released from AT in the heart, is an independent predictor of poor clinical outcome of heart failure patients. However, the underlying mechanisms involved in this process are incompletely understood.

The EU-funded HRS EAT (Epicardial adipose tissue as a regulator of myocardial biology: adiponectin signaling pathways) project proposed to investigate the interplay between AT and myocardium. The work focused on the molecular and functional impact of adiponectin on the heart and reciprocally on the identification of a paracrine signal from the myocardium to AT.

The consortium obtained samples from patients undergoing coronary artery bypass grafting to find clinical associations between adiponectin expression and myocardial redox state. They also performed ex vivo experiments to address the mechanisms regulating the interactions between AT and the heart. For this purpose, they also used a transgenic mouse model of the disease.

Results clearly demonstrated the bi-directionality of AT-heart association. In patients with ischaemic heart disease, the heart seems to transmit signals to the AT. AT in turn responds by upregulating the expression of protective genes such as adiponectin. This indicates that adiponectin acts as an antioxidant defensive mechanism against myocardial disease and could be exploited therapeutically.

Mechanistic insight into the process unveiled that myocardial oxidative stress leads to the formation of lipid oxidation products in the heart. These induce peroxisome proliferator-activated receptor (PPAR)-γ activation in human epicardial AT, which increases adiponectin expression.

Taken together, HRS EAT outcomes provide compelling evidence on the interaction of the myocardium and its surrounding AT. Results suggest that inducing PPAR-γ signalling and/or adiponectin in epicardial fat could have beneficial antioxidant effects on the failing myocardium of ischaemic heart disease patients.