LEP and obesity due to melanocortin 4 receptor deficiency: The potential reasons for these discrepancies among studies include: 1) Leptin resistance: the development of leptin resistance, a hallmark of obesity, may reduce signaling efficacy in target tissues despite hyperleptinemia, due to receptor desensitization or disruptions in cellular signaling pathways (6); 2) Dynamic nature of VEGF: VEGF levels may transiently rise under acute stress conditions such as inflammatory states or hypoxia (17,28,29).