Abstract
Adipose tissue is hyper-vascularized. Vessels in adipose tissue not only supply nutrients and oxygen to nourish adipocytes, but also provide cytokines that regulate mass and function of adipose tissue. Understanding the fundamental mechanisms how vessels modulate adipocyte functions would provide new therapeutic options for treatment of metabolic disease and obesity. In recent years, researches about ghrelin are focused on glucose and lipid metabolism, but its effect on vascular function remains uncharacterized. In the present study, ghrelin receptor gene deletion mice (Ghsr−/− mice) were used to study ghrelin-regulated vascular metabolism in white adipose tissue. Ghsr−/− mice demonstrated lower food intake, lower body weight, and resistance to high-fat diet-induced obesity. The number of vessels in white adipose tissue was decreased in Ghsr−/− mice when compared with wild type mice fed with high-fat diet. To further define ghrelin effects in vitro, we used endothelial progenitor cells from wild type and Ghsr−/− mice as well as human umbilical vein endothelial cells in our experiments. We found that ghrelin stimulated endothelial cells angiogenesis and migration through the MEK-ERK signaling pathway. [d-Lys3]-GHRP-6 and PD98059 could reverse the effects of ghrelin on endothelial cells. Our study indicates that ghrelin activates its receptor on endothelial cells to promote angiogenesis and migration via a mechanism involving the extracellular regulated protein kinases (ERK) signaling pathway.
Highlights
Adipose tissues are highly vascularized, brown adipose tissue (BAT) is one of the most vascularized tissues in the body [1,2,3]
Binding to its receptor- growth hormone secretagogue receptor 1a (GHSR1a), ghrelin plays a variety of biological effects, besides promoting the release of growth hormone, ghrelin stimulates food intake and regulates fat metabolism [15]
Wild type mice fed with 45% high fat diet (HFD) for 12 weeks demonstrated significant increases in body weight relative to animals fed normal chow diet (NCD)
Summary
Adipose tissues are highly vascularized, brown adipose tissue (BAT) is one of the most vascularized tissues in the body [1,2,3]. Vascular system plays a significant role in controlling adipose tissue mass and functions [5,6,7,8]. It controls the fat mass by altering the number of capillaries. Alterations of WAT mass and functions coordinated with angiogenesis or vascular regression, which are regulated by various types of growth factors, cytokines, and adipokines [7]. Understanding the molecular mechanisms that control adipose tissue angiogenesis may provide new vascular targets for the treatment of obesity and metabolic disorders [11,12]
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