Angiogenesis modulates adipogenesis and obesity

Abstract

Substantial evidence shows that neoplastic and nonneoplastic tissue growth is dependent on angiogenesis. Neovascularization and adipogenesis are temporally and spatially coupled processes during prenatal life and they continue to reciprocally interact via paracrine signaling systems throughout adult life. Activated adipocytes produce multiple angiogenic factors including leptin, angiopoietins, HGF, GM-CSF, VEGF, FGF-2, and TGF-beta, which either alone or collectively stimulate neovascularization during fat mass expansion. Thus antiangiogenic agents provide a novel therapeutic option for prevention and treatment of human obesity and its related disorders.

Figure 1. Regulation of adipose tissue angiogenesis by multiple factors.

Diversity of cell populations in the adipose tissue, including preadipocytes and adipocytes, ASCs, and inflammatory cells contributes to production of multiple angiogenic factors and inhibitors that regulate adipose angiogenesis. Interplay between different factors could result in angiogenic synergism. For example, leptin and VEGF-A or FGF-2 could synergistically stimulate angiogenesis. Tissue hypoxia could further upregulate expression levels of VEGF and leptin. MMPs could increase bioavailability of angiogenic factors by release of the matrix-bound VEGF.

Figure 2. Role of leptin in regulation of adipose angiogenesis.

Leptin directly induces angiogenesis by activation of its functional receptor, Ob-Rb, expressed on endothelial cells. In addition to its angiogenic activity, leptin is also able to induce vascular fenestrations and permeability. Leptin could indirectly induce angiogenesis via upregulation of VEGF expression.