Adipose tissue remodeling and obesity

Abstract

To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth.

Figures

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.

Figure 2. Healthy and unhealthy AT.

(A) Trichrome stain of a healthy murine epididymal fat pad with densely packed, hexagonal adipocytes and limited immune cell infiltration. (B) Trichrome stain of an unhealthy ob/ob epididymal fat pad, containing a high level of immune cell infiltration and enhanced ECM (blue areas). Scale bars: 50 μm.