Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Silvia Penuela

Abstract

The obesity epidemic is a growing concern due to its various comorbidities and associated risk factors. Pannexins 1 and 3 (Panx1 and Panx3), are members of a family of channel-forming glycoproteins that have been reported to be important in paracrine signaling and development. Panx1 and Panx3 are homologous and are regulated in many different cell types, mediating cell proliferation and differentiation. We have shown that Panx1 and Panx3 are expressed in adipocytes and adipose-derived stromal cells (ASCs) throughout the process of differentiation. Mice globally lacking Panx1 (Panx1 KO) have significantly greater total fat mass compared to wildtype (WT) mice under a normal diet. Comparatively, mice globally lacking Panx3 (Panx3 KO) have significantly less total fat mass compared to WT mice on the same diet. Multipotent ASCs isolated from both Panx1 KO and Panx3 KO mice proliferate less than WT cells. ASCs lacking Panx1 also have increased adipogenic differentiation and fat accumulation capacity compared to WTs. Despite the Panx1 KO mice having greater fat content, when placed on a high fat diet, they exhibit no differences in weight gain or metabolic parameters compared to WT mice. When placed in metabolic cages, Panx1 KO mice display significantly increased total activity, ambulatory activity, and sleep significantly less than WT mice. In contrast, Panx3 KO mice placed on a high fat diet exhibit a slight reduction in weight gain, however show no significant differences when placed in metabolic cages on regular diets. We conclude that both Panx1 and Panx3 are regulated throughout adipocyte proliferation and differentiation at early stages in the adipogenic lineage and can regulate fat accumulation in vivo, potentially playing contrasting roles.

Available for download on Thursday, August 16, 2018


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