Defense Date

2018

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Stefano Toldo

Second Advisor

Antonio Abbate

Third Advisor

Roland Pittman

Abstract

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting blood glucose, and attenuated cardiac diastolic dysfunction after WD compared to wild-type mice. Collectively, the metabolic and cardiac phenotypes of NCCKO mice resembled that of the IL-18KO mice, indicating that NCC may mediate IL-18 signaling in a mouse model of diet-induced obesity and cardiac dysfunction.

Rights

© Zachary Cutter

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-10-2018

Available for download on Friday, May 10, 2019

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