Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Physiology

Supervisor

Dr. S. Jeffrey Dixon

2nd Supervisor

Dr. David W. Holdsworth

Joint Supervisor

Abstract

P2X7 is an ATP-gated ion channel in the plasma membrane of a number of cell types. Previous in vitro studies show that P2X7 plays a role in regulating the differentiation of osteoblasts and adipocytes from mesenchymal precursors, as well as cellular metabolism and energy homeostasis. Furthermore, P2X7 has been implicated in mediating the effects of mechanical stimuli in bone. Our objective was to investigate the roles of P2X7, mechanical vibration, and their possible interaction in regulating body composition in vivo. We developed a novel method to monitor body composition during growth and aging in mice using micro-computed tomography (Chapter 2). This method permits rapid and reproducible quantification of adipose, lean and skeletal tissues in a non-invasive manner. We then applied this methodology to monitor the body composition of wild-type and P2X7 knockout mice (Chapter 3). Loss of P2X7 function led to greater adiposity and ectopic lipid accumulation in older male mice. We next investigated the effects of low-magnitude, high-frequency vibration on wild-type and P2X7 knockout mice (Chapter 4). Under our conditions, vibration does not induce changes in body composition or bone microarchitecture. Together, our studies provide an effective tool for characterizing whole-body composition of mice and establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism. Finally, our findings and those of others highlight the need to re-evaluate current thinking on the effects of low-magnitude, high-frequency vibration on body composition in vivo.


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