Excessive macronutrient intake in obesity can lead to adipocyte hypertrophy, hypoxia, or necrosis, triggering macrophage infiltration and activating various proinflammatory pathways such as c-Jun N-terminal kinase (JNK), IkappaB kinase (IKK), protein kinase R (PKR), and toll-like receptors. This evidence concerns the gene EIF2AK2 and obesity due to melanocortin 4 receptor deficiency.