Figure 1. Healthy and unhealthy AT expansion.

(A) Healthy AT expansion consists of an enlargement of AT through effective recruitment of adipogenic precursor cells to the adipogenic program, along with an adequate angiogenic response and appropriate remodeling of the ECM. There are strong individual differences with respect to the potential for AT expansion. (B) In contrast, pathological AT expansion consists of massive enlargement of existing adipocytes, limited angiogenesis, and ensuing hypoxia. As a result, HIF-1α is induced, which in turn can cause the induction of a fibrotic program. Ultimately, M1-stage macrophages prevail, leading to an inflammatory phenotype that is strongly associated with systemic insulin resistance.