Honors Theses
Date of Award
5-2026
Document Type
Undergraduate Thesis
Degree Name
BS
Department
Biomedical Sciences
Faculty Mentor
Wito Richter, Ph.D.
Advisor(s)
Lucia Plant, Ph.D., Nancy Rice, Ph.D., Mohini Kamra, Ph.D.
Abstract
The cAMP-phosphodiesterase 4 (PDE4) family comprises four genes, PDE4A, B, C, and D. Treatment with non-selective PAN-PDE4 inhibitors induces weight loss and improves glucose homeostasis in humans and animals, suggesting a therapeutic potential of targeting PDE4s in obesity and metabolic syndromes. However, these drugs also produce gastrointestinal adverse effects that limit their clinical utility. Conversely, targeting individual PDE4 subtypes is a promising approach to separate the therapeutic benefits from the side effects of current PAN-PDE4 inhibitors. Prior research has shown that mice with a global genetic deletion of PDE4D mimic the metabolic phenotype produced by PAN-PDE4 inhibitor treatment, including reduced body weights and adiposity, and improvements in blood glucose homeostasis. However, global PDE4D-knockout mice (4DKO) are runts at birth - weighing significantly less and experiencing high rates of neonatal mortality - opening the possibility that the lack of PDE4D during fetal development may contribute to or predispose toward the metabolic phenotype of the mice, whereas inhibition of PDE4D in an adult mouse, or an obese human, may not reverse obesity or metabolic abnormalities. To address this question, I utilized a novel mouse model that employs the Cre/loxP system to allow the timed ablation of PDE4D upon treatment of adult mice with tamoxifen. Characterizing their metabolic phenotype revealed that the tamoxifen-induced ablation of flox-PDE4D in adult mice replicates the core features of global 4DKO mice, including reduced body weights and adiposity, and improved glucose homeostasis, suggesting that targeting PDE4D may represent a novel therapeutic approach for obesity and metabolic syndromes.
Recommended Citation
Chancey, Zacharay L., "Type 4D Cyclic AMP-Phosphodiesterase (PDE4D) as a Potential Novel Therapeutic Target in Metal" (2026). Honors Theses. 164.
https://jagworks.southalabama.edu/honors_college_theses/164
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