Abstract: TH-PO322
GDF15 Is Necessary for the Physiological Adaptation to Hypokalemia
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders
- 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic
Authors
- Lasaad, Samia, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Walter Lamouroux, Christine, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Rafael, Chloe, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Morla, Luciana, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Doucet, Alain, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Picard, Nicolas, Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRS, University Lyon 1, Lyon, France
- Blanchard, Anne, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Crambert, Gilles, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
- Cheval, Lydie, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Laboratoire de Physiologie Rénale et Tubulopathies, Pais, France
Background
Population in industrialized countries consume less potassium (K+) than recommended and this may, in the long term, contribute to the development of cardiovascular pathologies. To face a K+ restriction, and avoid hypokalemia two synergistic mechanisms are induced by our organism. The external regulation adapting the renal and fecal excretion of K+ to the intake and the internal regulation controlling the storage or release of K+ from cellular compartment (muscle). The kidney adapts its function to retain K+ by increasing the number of type-A intercalated cells (ICA). A transcriptomic analysis, we published a few years ago, revealed that the TGFβ-related growth factor GDF15 was upregulated in renal collecting ducts of K+ depleted animals. We hypothesize that GDF15 may have an impact on both the external and internal balance of K+ homeostasis and is therefore necessary to the physiological adaptation to hypokalemia.
Methods
We used C57BL6J mice wild type or knockout for the Gdf15 gene, put on a control or low-K+ diet. Metabolism cages were used for metabolic analysis. Number of ICA was determined by immunofluorescence on microdissected tubules. Muscle mass was assessed by TD-NMR. Urine samples of healthy human volunteers (HHV), K+ depleted or not for a week, were collected from a previous study and GDF15 expression was analyzed by ELISA.
Results
Under a K+ depletion we showed: 1/ an increase of Gdf15 expression along the nephron, mostly in the collecting duct, and in the intestine, plasma and urine of mice, 2/ a relationship between GDF15 levels and K+ restriction in HHV, 3/ a delayed renal adaptation in GDF15-KO mice, leading to hypokalemia. The adaptation issue is partly explained by the absence of proliferation of ICA. The renal effect of GDF15 depends on the ErbB2 receptor. Finally, we demonstrated that GDF15 also regulates the internal balance by inducing a loss of muscle, releasing K+ in the plasma.
Conclusion
Altogether, these results demonstrate that GDF15 is a key factor that orchestrates synergetically both the regulation of the internal and external potassium balance.
Funding
- Government Support – Non-U.S.