INS and obesity due to melanocortin 4 receptor deficiency: Chronic inflammation (CI), often originating from adipose tissue in obesity, releases excessive free fatty acids, reactive oxygen species, and pro-inflammatory cytokines (29), which interfere with insulin signaling, worsen IR (30), increase the risk of plaque rupture and thrombosis (31), and drive the progression of NAFLD from simple steatosis to non-alcoholic steatohepatitis (NASH) (32).