Author

Mengcheng Liu

Date of Award

Summer 8-2020

Document Type

Thesis

Department

Molecular Science and Nanotechnology

Abstract

Obesity is the leading cause of chronic disease and has contributed to significant health problems and complications. In order to solve this increasingly serious social problem, it is particularly important to deepen the understanding of the biological causes of obesity. Obesity is the result of an increased mass of adipose tissue after excessive caloric intake, and adipogenesis is the main strategy through which the body increases the number of adipocytes. However, due to the lack of research, the current understanding of adipogenesis is not enough to yield results in the clinic.

The regulation of adipogenesis is complex, and the role of the Notch signaling pathway in adipogenesis has long been controversial, as the role of individual Notch receptors appears to vary with experimental conditions. In this dissertation, we demonstrate that in human adipose-derived stem/stromal cells (hADSCs), Notch1 and Notch3 have distinct expression profiles and roles during adipogenesis. Expression of these Notch receptors changed during adipogenesis with Notch3 expressed prior to the formation of lipid vesicles and Notch1 only appearing after vesicle formation. In addition, the siRNA-mediated Notch3 knockdown demonstrated an increased expression of PPARγ, an adipogenic marker, which was paralleled by a marked decrease in expression of β-catenin, the key functional component of the canonical Wnt/β-catenin signaling pathway. This study deepens the understanding of Notch signaling by clarifying the distinct roles of Notch1 and Notch3 during adipogenesis offering a novel therapeutic target for research aimed at obesity and diabetes.

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