TNF and obesity due to melanocortin 4 receptor deficiency: Obesity-induced adipose tissue dysfunction leads to systemic chronic low-level inflammation, where adipocytes and CAFs release abundant pro-inflammatory factors (e.g., IL-6, Tumor Necrosis Factor-α (TNF-α)) and adipokines (e.g., leptin, adiponectin), thereby remodeling the TME and facilitating pre-metastatic niche formation.