Date on Master's Thesis/Doctoral Dissertation

12-2014

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Committee Chair

Hill, Bradford G.

Committee Co-Chair (if applicable)

Bhatnagar, Aruni

Committee Member

Joshua, Irving G.

Committee Member

Schuschke, Dale A.

Committee Member

Miller, Cynthia J.

Subject

Tissue remodeling; Stem cells

Abstract

The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters outlining the adipose tissue remodeling process, metabolic changes which occur in adipose tissue in response to nutrient excess, diet-induced variations in adipose tissue stem cell distribution, and the impact of stem cell transplantation on remodeling of adipose tissue. Chapter one serves as a general introduction defining the development of obesity, health implications of obesity and methods by which adipose tissue can remodel in response to nutrient excess. Chapter two describes the metabolic changes that occur within visceral adipose tissue upon consumption of high fat diet. The third chapter details changes in adipose tissue stem cell distribution in response to nutrient excess. The studies presented in chapter three suggest that obesity is associated with an imbalance in adipocyte and endothelial progenitor cells. This imbalance was corrected to determine if doing so was sufficient to ameliorate obesity-associated complications and data from these studies are presented in chapter four. Finally, a comprehensive discussion of the implications of these studies is outlined in chapter five. Chapters two and three focus on the impact of high fat diet on the metabolic profile of adipose tissue and distribution of adipose tissue stem cells. Chapter four centers on correcting the progenitor cell ratio, skewed by consumption of high fat diet. The studies presented in the fourth chapter suggest increasing the endothelial progenitor cell population promotes cell engraftment into vasculature of the adipose tissue. Increasing the capacity of these cells further supports vessel formation and engraftment in obese tissue and may therefore offer insight into potential therapeutic treatments.

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