Obesity

Obesity is a chronic, relapsing, multifactorial disease characterized by excess adiposity that impairs health. White adipose tissue (WAT) functions as an endocrine organ secreting adipokines that regulate metabolism, inflammation, and appetite. In obesity, adipocyte hypertrophy leads to hypoxia, macrophage infiltration, and a pro-inflammatory state with elevated TNF-alpha, IL-6, and resistin, while protective adiponectin levels decline. Adiponectin normally enhances insulin sensitivity via AMPK activation and fatty acid oxidation; its reduction in obesity directly contributes to insulin resistance. Leptin, secreted proportionally to fat mass, signals satiety via hypothalamic leptin receptors (ObRb) activating JAK-STAT3 pathways. In obesity, chronic hyperleptinemia causes leptin resistance through SOCS3-mediated suppression of leptin signaling, impairing satiety and promoting continued energy intake despite adequate fat stores. Insulin resistance in obesity involves impaired insulin receptor substrate (IRS-1) phosphorylation by serine kinases activated by free fatty acids, inflammatory cytokines, and ER stress. Ectopic lipid deposition in liver (NAFLD/NASH), skeletal muscle, and pancreatic beta cells (lipotoxicity) further impairs glucose homeostasis. Visceral adiposity is particularly metabolically active, draining directly into the portal circulation and exposing the liver to high concentrations of free fatty acids...