Key Points

• Obesity has a genetic basis as well as environmental and behavioral origins
• Age contributes to a shift in balance between fat and muscle mass
• Various negative feedback loops contribute to obesity
  • Increased caloric intake and reduced physical activity
    • Alters energy homeostasis, leading to a reduced metabolic rate
    • Alters neurohormonal signals, leading to increased appetite
  • Increased visceral adiposity
    • Promotes insulin resistance
    • Promotes inflammation
      • Worsens insulin resistance
      • Leads to macrophage mobilization into adipose tissue, which worsens inflammation
    • Together, inflammation and insulin resistance contribute to development of cardiovascular disease, type 2 diabetes, cancer, and other poor outcomes