Figure 1.

Working model for the development of fibrosis and inflammation in obese adipose tissue. In lean adipose tissue, the adipocytes are small and healthy. Adequate blood vessels formed by proper angiogenesis provide oxygen, hormones, nutrients, and adipocyte precursors to support the healthy expansion of the tissue (A); during diet-induced obesity, adipose tissue expands rapidly through hyperplasia and hypertrophy. Meanwhile, new blood vessel formation cannot keep up with the expansion, the adipocytes become larger, and local hypoxia thus develops (B); At the late phase of obesity, hypoxia stimulates massive fibrosis. The mechanical stress induced by the overdeveloped ECM leads to necrosis of the adipocytes. As a result, macrophages are accumulated and polarized to the M1 subtype in the tissue. They form “crown-like” structures in obese adipose depots. The local fibrosis and inflammation further lead to the whole-body insulin resistance (C). Of note, not all the adipose tissue expansion has “unhealthy” consequences. In addition to the calorie excess, genetic variants and environmental factors also have profound effects on the expansion.