DOI
https://doi.org/10.25772/DSMT-MX19
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
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Circulatory and Respiratory Physiology Commons, Translational Medical Research Commons