Figure 3. Phenotypic modulation of adipose tissue.

Adipose tissue can be described by at least three structural and functional classifications: lean with normal metabolic function, obese with mild metabolic dysfunction and obese with full metabolic dysfunction. As obesity develops, adipocytes undergo hypertrophy owing to increased triglyceride storage. With limited obesity, it is likely that the tissue retains relatively normal metabolic function and has low levels of immune cell activation and sufficient vascular function. However, qualitative changes in the expanding adipose tissue can promote the transition to a metabolically dysfunctional phenotype. Macrophages in lean adipose tissue express markers of an M2 or alternatively activated state, whereas obesity leads to the recruitment and accumulation of M1 or classically activated macrophages, as well as T cells, in adipose tissue. Anti-inflammatory adipokines, including adiponectin and secreted frizzled-related protein 5 (SFRP5), are preferentially produced by lean adipose tissue. In states of obesity, adipose tissue generates large amounts of pro-inflammatory factors, including leptin, resistin, retinol-binding protein 4 (RBP4), lipocalin 2, angiopoietin-like protein 2 (ANGPTL2), tumour necrosis factor (TNF), interleukin-6 (IL-6), IL-18, CC-chemokine ligand 2 (CCL2), CXC-chemokine ligand 5 (CXCL5) and nicotinamide phosphoribosyltransferase (NAMPT). Obese individuals with adipose tissue in a metabolically intermediate state have improved metabolic parameters, diminished inflammatory marker expression and better vascular function compared with individuals that have metabolically dysfunctional adipose tissue. Metabolically dysfunctional adipose tissue can be associated with higher levels of adipocyte necrosis, and M1 macrophages are arranged around these dead cells in crown-like structures.