REN and obesity due to melanocortin 4 receptor deficiency: However, it must be stressed that not only hemodynamic, but also obesity-related metabolic factors, like activation of the renin–angiotensin–aldosterone and sympathetic nervous systems, local and systemic inflammation, hyperinsulinemia, hyperleptinemia, and possibly lipotoxicity, may adversely affect the LA wall and therefore favoring the risk of atrial arrhythmia [43, 44].