Presence of vasculature results in faster insulin response in adipocytes in vascularized adipose tissue model

Abstract

Besides being an energy store, adipose tissue is an endocrine organ closely associated with the vascular system. Human relevant in vitro models are needed to study adipose tissue and related diseases. Vasculature plays a central role in the development and inhibition of adipose tissue-related diseases.
Here, an adipocyte culture was established from hASC (human adipose stromal cells), and a vascularized adipose tissue model was established from hASC and HUVEC (human umbilical cord vein endothelial cells) co-culture, utilizing the same differentiation procedure. Comparing these models allowed analysis of the effect of vascularization on adipocytes. Both models were characterized on gene (adipocyte and vasculature-related), protein (von Willebrand factor, collagen IV, CD140b and CD144, secretion of leptin, adiponectin and FABP4), and functional (triglyceride accumulation, glucose uptake, and lipolysis) levels. Additionally, the vascularized adipose tissue model was exposed to chemicals with known effects on adipogenesis and angiogenesis (rosiglitazone, chlorpyrifos, prochloraz, mancozeb, butylparaben, 15-deoxy- Δ12,14-prostaglandin J2, bisphenol A, bis-(2-ethylhexyl) phthalate, tributyltin chloride) to compare their effects to the literature. The in vitro vascularized adipose tissue model demonstrated the presence of functional adipocytes and an extensive vascular network, displaying relevant gene and protein markers. Insulin induced glucose uptake, inhibited lipolysis, and influenced vasculature-related genes. The presence of vasculature led to a faster lipolysis inhibition by insulin and modulated responses to chemicals. This novel, thoroughly characterized, vascularized adipose tissue model is a promising new tool for studying adipose tissue as well as the effects of chemicals on adipogenesis and angiogenesis in adipose tissue.