A recent study conducted by He et al. demonstrated that leucine-rich alpha-2-glycoprotein 1 (LRG1), an adipokine associated with obesity, inhibits hepatic insulin signaling by downregulating IRS-1 and IRS-2, thereby exacerbating high-fat diet-induced insulin resistance [72]. This evidence concerns the gene LRG1 and obesity due to melanocortin 4 receptor deficiency.