Author ORCID Identifier
https://orcid.org/0009-0000-4639-4285
Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Dr. Christopher D. Green
Abstract
Spinster homolog 2 (Spns2) exports sphingosine-1-phosphate (S1P) and imports glucose in order to regulate cellular responses in the liver. Defined by the term liver zonation, the liver facilitates glucose and lipid homeostasis by spatially organizing itself into different regions that compartmentalize metabolism so that all its opposing processes can coincide simultaneously. S1P also accumulates in mice and humans upon overnutrition and Western diet (WD). When undergoing a metabolic stressor such as a WD, liver zonation can be perturbed, creating a heterogeneous microenvironment for metabolic liver diseases to develop. Although Spns2 was recently implicated in liver disease, very little is known about its role in lipid and glucose metabolism in the liver, including how Spns2 is expressed across the lobule and whether its expression displays any sex-specific differences in mice. Using techniques such as immunofluorescence imaging, fluorescence-activated cell sorting, and in vivo Spns2 deletion, we show that Spns2 specifically exists in the periportal region of the lobule colocalized with the periportal zonal marker E-Cadherin. We demonstrate that upon a Western diet, Spns2 expression is decreased along the periportal-pericentral axis in male mice but not in female mice, suggesting a potential sex-difference in the response to metabolic stress. Finally, we show no significant differences in blood glucose upon a glucose tolerance test in control and Spns2 -/- male mice. In conclusion, this study demonstrates the zone-specific expression and potential function of inside out S1P signaling via Spns2. Ultimately, understanding the role of Spns2 and S1P signaling in the liver may be relevant for the therapeutic treatment of liver-related pathologies.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-23-2026