Adipogenesis and angiogenesis : roles in tissue engineering and glucose metabolism

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 118-127).Adipose tissue serves two main functions in the body: (1) it is the body's primary energy depot; and (2) it also serves as an important endocrine organ, producing and secreting various enzymes, growth factors, cytokines, and hormones. Both of these functions require ample access to circulating blood. Many aspects of angiogenesis during adipose tissue expansion remain poorly understood. Adipocytes produce a large variety of molecules involved in angiogenesis, and obesity is associated with elevated circulating levels of Vascular Endothelial Growth Factor (VEGF). Our lab has previously shown that angiogenesis and adipogenesis are mutually dependent via a VEGF receptor 2 (VEGFR2)-mediated mechanism. Since then several other studies have reinforced a role for the VEGF-VEGFR system in energy metabolism. For example, genetically obese mice treated with anti-VEGF antibody had lower fat pad weights, but the VEGF receptor responsible for this observation is not known. There is also disagreement on the cell type(s) responsible for fat tissue's angiogenic capability, with some studies supporting a dominant role for adipocytes, while others attribute most of the angiogenic capacity to the adipose tissue stromal cells (ASC). This thesis project aimed to fill some of these gaps by examining the angiogenic capacity of adipose tissue relative to other tissues, the effects of VEGFR-1 and R-2 blockade in mouse models of adipogenesis and diet-induced obesity, the respective angiogenic capabilities of adipocytes and ASC, and the possibility of harnessing the angiogenic potential of adipose tissue for vascular tissue engineering.(cont.) In addition, a physiologically-based mathematical model was developed to simulate the regulatory effects of the leptin pathway on murine energy homeostasis.by Joshua Tam.Ph.D