Adipose tissue angiogenesis1,2

Abstract

A review of adipose tissue angiogenesis includes the morphological and cytochemical development of adipose tissue vasculature and the concept of primitive fat organs. Spatial and temporal relationships between fetal vascular and fat cell development are discussed, including depot- and genetic-dependent arteriolar differentiation. The relationship between connective tissue deposition and elaboration of adipose tissue vasculature is discussed with respect to regulating adipocyte development in a depot-dependent manner. In vitro studies indicated that depot-dependent vascular traits may be attributable to intrinsic growth characteristics of adipose tissue endothelial cells. These studies indicate that adipogenesis may be regulated by factors that drive angiogenesis. Fundamental aspects of angiogenesis, including basement membrane breakdown, vasculogenesis, angiogenic remodeling, vessel stabilization, and vascular permeability were reviewed. Critical angiogenic factors include vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins (Ang), ephrins, matrix metalloproteinases, and the plasminogen enzymatic system. Vascular endothelial growth factor is the most critical factor because it initiates the formation of immature vessels and disruption of a single VEGF allele leads to embryonic lethality in mice. Expression of VEGF is influenced by hypoxia, insulin, growth factors, and several cytokines. Angiogenic factors secreted and/or produced by adipocytes or preadipocytes are discussed. Vascular endothelial growth factor expression and secretion by adipocytes is regulated by insulin and hypoxia, and is associated with adipose tissue accretion. Vascular endothelial growth factor accounts for most of the angiogenic activity of adipose tissue. The proposed role of leptin as an adipogenic factor is reviewed with respect to efficacy on various aspects of angiogenesis relative to other angiogenic factors. The VEGF and leptin genes are both hypoxia inducible, but potential links between VEGF and leptin gene expression have not been examined. Finally, several studies including a study of mice treated with antiangiogenic factors indicate that adipose tissue accretion can be controlled through the vasculature per se.

Autologous In Vivo Adipose Tissue Engineering in Hyaluronan-Based Gels—A Pilot Study

“…The adipose tissue was found around mature vessels in addition to newly formed small vascular structures. These findings are in complete accordance with the literature, where a close association between adipogenesis and angiogenesis is stated [28]. In HYADD4, in contrast to HYADD3, no fat formation was observed in any specimen, and there was higher cellularity than in the HYADD3 samples.…”

Decorin is a secreted protein associated with obesity and type 2 diabetes

“…As angiogenesis is markedly upregulated within the adipose tissue during obesity, 20,22 the increased decorin gene expression in adipose tissue from obese P. obesus is consistent with a role for decorin in angiogenesis. Several studies have supported a proangiogenic role for decorin and, in particular, in angiogenesis associated with inflammatory conditions.…”

“…19,20 To accommodate these changes, remodelling of the ECM occurs by degradation of the existing ECM and production of new ECM. As decorin is required for the correct folding of other ECM components such as collagen, 21 the elevated levels of decorin expression in adipose tissue from obese IGT and T2D P. obesus raises the possibility that decorin expression may be induced in adipose tissue in the obese state to facilitate new ECM structures forming within the expanding adipose tissue.…”

Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans

“…Additionally, leptin correlated negatively with TPR and positively with C W , implicating leptin as a possible role player in the accommodating effect observed in the obese Caucasian group, but not in the obese African group. One may speculate that this accommodating effect could be the result of leptin's angiogenic 37,38 and/or vasodilatory [18][19][20] effect, which would lead to decreased TPR and increase C W .…”