Interaction of Adipogenesis and Angiogenesis in Dietary-Induced Obesity.

Abstract

Chronic overnutrition and lack of physical activity result in excess deposition of adipose tissue and insulin resistance, which play key roles in the pathophysiology of type 2 diabetes and associated cardiovascular disease (1). The expansion of adipose tissue mass in dietary-induced obesity involves both hyperplasia and hypertrophy of adipocytes, and these processes are associated with extensive neovascularization mediated by the sprouting of endothelial cells (ECs) from preexisting blood vessels (2). Normal angiogenesis depends on the intricate balance between angiogenic factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factors, and transforming growth factor-β, as well as angiostatic factors, such as angiostatin, endostatin, and the thrombospondins (3). Under chronic overnutrition and obesity, adipocytes produce EC-specific mitogens and angiogenic factors that favor vessel formation. Furthermore, ECs produce growth factors and cytokines that increase adipogenesis and fat deposition (4,5). Thus, adipocytes and ECs interact to regulate both adipogenesis and angiogenesis, and this interaction prompts the expansion of the capillary bed in conjunction with expanding regional adipose depots. Adipogenesis is promoted by a network of transcription factors, including the CCAAT/enhancer–binding proteins (C/EBP)β, C/EBPδ, C/EBPα, and peroxisome proliferator–activated receptor γ (PPARγ) (6) (Fig. 1). Research from our laboratory has confirmed that mammalian target of rapamycin (mTOR)/ribosomal S6 kinase (S6K1) activation is enhanced under conditions of overnutrition (1) and impacts on PPARγ-C/EBPα …