Abstract
Obesity is a worldwide health problem, and as its prevalence increases, so does the burden of obesity-associated co-morbidities like type 2 diabetes or cardiovascular diseases (CVDs). Adipose tissue (AT) is an endocrine organ embedded in a dense vascular network. AT regulates the production of hormones, angiogenic factors, and cytokines. During the development of obesity, AT expands through the increase in fat cell size (hypertrophy) and/or fat cell number (hyperplasia). The plasticity and expansion of AT is related to its angiogenic capacities. Angiogenesis is a tightly orchestrated process, which involves endothelial cell (EC) proliferation, migration, invasion, and new tube formation. The expansion of AT is accelerated by hypoxia, inflammation, and structural remodeling of blood vessels. The paracrine signaling regulates the functional link between ECs and adipocytes. Adipocytes can secrete both pro-angiogenic molecules, e.g., tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or vascular endothelial growth factor (VEGF), and anti-angiogenic factors, e.g., serpins. If the pro-angiogenic molecules dominate, the angiogenesis is dysregulated and the endothelium becomes dysfunctional. However, if anti-angiogenic molecules are overexpressed relative to the angiogenic regulators, the angiogenesis is repressed, and AT becomes hypoxic. Furthermore, in the presence of chronic nutritional excess, endothelium loses its primary function and contributes to the inflammation and fibrosis of AT, which increases the risk for CVDs. This review discusses the current understanding of ECs function in AT, the cross-talk between adipose and ECs, and how obesity can lead to its dysfunction. Understanding the interplay of angiogenesis with AT can be an approach to therapy obesity and obesity-related diseases such as CVDs.
Highlights
Recent findings have led us to reconsider the notion of adipose tissue (AT) being a mere storage depot for body energy
Tang et al identified the presence of white adipocyte progenitors in the mural compartment of adipose vasculature, but not in the vasculature of other tissues. These mural cells had high adipogenic potential (Tang et al, 2008). These results indicate a link between endothelial cell (EC) and adipocytes in terms of their interchangeability in the presence of a possible “switch” and the cell–cell interaction
The VEGFR1 knockout significantly ameliorated obesity-induced dysfunction by lowering the levels of free fatty acids (FFAs), glycerol, triglyceride, glucose, and insulin in the blood of these mice (Seki et al, 2018). These results demonstrate the regulatory role and crosstalk between the different vascular endothelial growth factor (VEGF)-members and their receptors that are involved in various mechanisms (Elias et al, 2013)
Summary
Recent findings have led us to reconsider the notion of adipose tissue (AT) being a mere storage depot for body energy. Activation of HIF-signaling pathways in macrophages in obese mice leads to induction of platelet-derived growth factor (PDGF) expression, which is likely to induce the tube formation of ECs to improve vascular density (Pang et al, 2008). Overexpression of VEGF in WAT and BAT in mice led to increased number and size of blood vessels, increased insulin sensitivity, and improved glucose tolerance (Elias et al, 2012).
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