Abstract: SA-PO0901
N-Acylphosphatidylethanolamine-Specific Phospholipase D Restrains SGLT-Associated Renal Glucose Reabsorption During Dehydration Stress
Session Information
- Health Maintenance, Nutrition, and Metabolism
October 24, 2026 | Location: Exhibit Hall A, 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
- Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Davies, Sean Stephen, Vanderbilt University, Nashville, Tennessee, United States
- Dikalov, Sergey, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Dikalova, Anna, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) is widely expressed and regulates lipid metabolism in brain, heart, and liver. Although NAPE-PLD deletion in adipocytes or hepatocytes impairs glucose tolerance and increases blood glucose, whether NAPE-PLD regulates renal glucose handling is unknown. We tested the hypothesis that NAPE-PLD modulates renal glucose handling.
Methods
Napepld knockout mice (Napepld-/-; KO) and wild-type (WT) controls were stressed by 23h water deprivation. NAPE-PLD expression and localization were assessed by immunostaining, and lipid distribution by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Physiological and biochemical parameters were compared at baseline and after water deprivation including urinary glucose concentration, glucose excretion, and fractional glucose reabsorption. SGLT2 and SGLT1 expression was measured by Western blot in cortical and outer medullary lysates.
Results
NAPE-PLD was prominently expressed in loop of Henle, collecting ducts, and proximal tubules in WT. At baseline, MALDI-MSI showed reduced LPC/PC lipid species, annotated as PC (16:0/0:0) & (18:0/0:0) in inner medulla and corticomedullary regions of KO kidneys. Baseline physiological parameters, including body weight, blood pressure, urine volume & sodium excretion, and blood glucose were not different. After water deprivation, both KO and WT had comparable changes in weight, pressure, urine volume & osmolality, and sodium excretion. Critically, water deprivation significantly increased serum glucose, that was accompanied by reduced urinary glucose, reduced glucose excretion rate, and increased fractional glucose reabsorption in KO mice vs WT. Consistent with enhanced tubular glucose reclamation, Western blot showed increased SGLT2 expression in the cortex and increased SGLT1 expression in the outer medulla of KO kidneys in water deprived mice. Upregulation of SGLT1 and glucose metabolism in KO mice occurred with increased kidney oxidative stress measured by Electron Spin Resonance+TMH spin probe.
Conclusion
These data reveal that NAPE-PLD regulates structural renal LPC/PC lipids and controls region-specific increases in cortical SGLT2 and outer medullary SGLT1. The findings identify NAPE-PLD as a previously unrecognized regulator of tubular glucose homeostasis and oxidative stress in conditions with renal stress/injury.
Funding
- NIDDK Support