LEP and major depressive disorder: Furthermore, immune challenges can activate adipose tissue hypertrophy, inflammation, macrophage infiltration, and secretion of pro-inflammatory cytokines such as leptin, interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) [65,66,67], leading to inflammation in the brain and potentially triggering depression [46].