INS and obesity due to melanocortin 4 receptor deficiency: Obesity leads to dysregulated adipocytes, which secrete an imbalance of adipokines (such as leptin and insulin), metabolites (such as cholesterol and free fatty acids), and cytokines (such as TNFα and interleukins), which can induce endocrine therapy resistance by activating various signal transduction pathways and regulating apoptosis-related genes [14,45].