INS and obesity due to melanocortin 4 receptor deficiency: High-nutrient conditions of obesity can shift ATMs from M2 to M1 through mTORC1, exacerbating insulin resistance.912–914 Intermittent fasting enhances visceral adipose tissue LPS-associated macrophage inflammatory phenotype through p53-driven adipocyte apoptosis, and inhibiting p53 prevents the accumulation of lipid-associated macrophages, enhancing systemic metabolic flexibility and insulin sensitivity.915 The NOTCH signaling pathway is a protective factor against insulin resistance.916 Recent studies have shown that IgG, an aging factor, can promote insulin resistance.