TNF and obesity due to melanocortin 4 receptor deficiency: The American College of Cardiology emphasizes obesity as a major risk factor for HFpEF through chronic inflammation and metabolic dysregulation [5], with adipose tissue expansion, macrophage infiltration, and cytokine release (e.g., TNF-α, IL-6, MCP-1) driving insulin resistance, diabetes, and cardiovascular and renal complications [6,7].