Abstract: FR-PO1087
Lymphatic Vessel Dysfunction Drives Impaired Lipid Clearance and Visceral Fat Accumulation During Steroid Treatment
Session Information
- Health Maintenance, Nutrition, and Metabolism
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Liu, Jing, Tongji Hospital Affiliated to Tongji University, Shanghai, China
- Rock, Charmaine R, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Shelton, Elaine L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Glucocorticoids (GCs) are widely used to treat kidney diseases but are associated with metabolic side effects, including visceral fat accumulation. Lymphatic vessels, composed of lymphatic endothelial cells (LECs) and lymphatic muscle cells (LMCs), are key participants in lipid homeostasis. This study was designed to understand how GCs affect lymphatic structure and function and contribute to visceral adiposity.
Methods
Rats received IP injections of dexamethasone (DEX) or vehicle for two weeks. In vivo clearance of Evans Blue dye was used to assess lymphatic function. Isolated lymphatic collecting vessels were used in pressure myography assays to assess pumping dynamics and permeability. Cultured LECs and LMCs were used in RNAseq studies, tube formation, and transepithelial electrical resistance assays.
Results
DEX-treated rats developed increased perirenal fat mass and adipocyte density. DEX decreased lymphatic vessel density in the kidney and in perirenal fat and impaired LEC tube formation. RNA sequencing in LECs found DEX upregulated cell junction genes (TJP1, Ocln), corresponding to increased transepithelial electrical resistance, indicating enhanced barrier integrity. Isolated DEX-treated lymphatic collecting vessels also had reduced permeability. In cultured LMCs, DEX reduced expression of L-type calcium channel gene, Cacna1c, contractility-related kinesin, and myosin genes, but increased expression of T-type calcium channel gene, Cacna1h. In myography studies using renal collecting vessels, DEX exposure diminished the magnitude of contraction but increased the frequency of spontaneous vessel contractions, consistent with the observed changes in contractility and pacemaker genes. Importantly, DEX-treated rats had delayed clearance of Evans Blue from ears compared to controls, which strongly correlated to the above-described alterations in lymphatic permeability and pumping dynamics.
Conclusion
DEX exposure promoted visceral fat accumulation. DEX disrupted lymphatic function by reducing vessel density, decreasing LEC permeability, and diminishing pumping dynamics, resulting in impaired Evans Blue clearance. We propose that these alterations impair lipid clearance and underlie GC-associated visceral adiposity.
Funding
- NIDDK Support