Adipose tissue.
Adipose tissue insulin resistance and dysfunctional lipid storage in adipocytes are sentinel events in the progression toward metabolic dysregulation with obesity. Forced expansion of adipose tissue by transgenic overexpression of the adipokine adiponectin prevents metabolic disease despite massive obesity (37). Impaired lipogenic/adipogenic capacity is associated with increased visceral fat in obese adolescents (38), and smaller omental adipocytes is a feature of metabolically healthy obese adults (39). These findings support the model that lipid “spillover” from fat promotes metabolic disease by fostering ectopic lipid deposition. Since an estimated excess of 20–30 million macrophages accumulate with each kilogram of excess fat in humans, one could argue that increased adipose tissue mass is de facto a state of increased inflammatory mass