CCN2 and obesity due to melanocortin 4 receptor deficiency: Obesity and insulin resistance also lead to the activation of the renin-angiotensin-aldosterone system (RAAS), transforming growth factor beta (TGF-β), connective tissue growth factor (cTGF) and endothelin-1, all leading to interstitial collagen deposition and subsequent defects of atrial conduction due to a substrate favoring re-entry and AF perpetuation [32].