REN and obesity due to melanocortin 4 receptor deficiency: HFD promotes obesity and activates key signaling pathways including the renin–angiotensin–aldosterone system, TGF-β, connective tissue growth factor, and endothelin-1 activation can lead to increased interstitial collagen deposition and cardiac tubular fibrosis, which may disrupt atrial conduction, leading to AI [73,74].