Semester of Graduation

Fall 2022

Degree

Master of Biological Science (MBioSci)

Department

Biological Sciences

Document Type

Thesis

Abstract

Obesity is a metabolic disorder that has turned into a global epidemic over the past few decades. Adipocyte dysfunction brought on by obesity can lead to increased risk of metabolic diseases such as cardiovascular disease and type 2 diabetes mellitus (T2DM). Knowing how adipocytes function to regulate metabolic homeostasis is critical. CUZD1 (CUB and Zona Pellucida-like Domain-containing protein 1) has not been studied in the context of adipocyte biology but could play a role in several metabolic processes. CUZD1 has been suggested to be a biomarker for several inflammatory diseases and cancers but little functional data has been published. There is some evidence that CUZD1 can associate with STAT5 in mammary tissue. Novel research of CUZD1 in adipocytes could provide more insight into how adipocytes control whole-body homeostasis. To start understanding the role of CUZD1 in adipocytes, we examined its tissue localization along with its subcellular localization and observed that CUZD1 is expressed in the adipocyte nucleus. Using the cultured 3T3-L1 model system, we examined CUZD1 expression over a time course of adipogenesis as well as CUZD1 stability over a 2 hour period. Mouse models were used to explore CUZD1 expression patterns in different nutritional states. In mesenteric white adipose tissue (mWAT), CUZD1 expression was downregulated in the fasting state compared to the fed state. High-fat and low-fat feeding had no effect on CUZD1 expression. Immunoprecipitation was utilized to determine if STAT5 could be present in a protein complex with CUZD1. We observed that STAT5A interacted with CUZD1 following growth hormone (GH) stimulation. A mouse model lacking adipocyte STAT5 was used to examine if loss of adipocyte STAT5 had an effect on the expression of CUZD1. In inguinal white adipose tissue (iWAT) of female mice, increased expression of CUZD1 was observed in the STAT5 knockout model. Collectively, these studies suggest that CUZD1 may be involved in hormonal signaling by modulating the JAK/STAT pathway. Overall, the role CUZD1 plays in adipocyte biology remains unknown but this data provides the first steps toward its understanding.

Date

8-7-2022

Committee Chair

Stephens, Jacqueline M.

DOI

10.31390/gradschool_theses.5647

Included in

Biology Commons

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