Renal adaptation to Western Diet: a crucial role for renal intercalated cells – FateForA

The kidneys have a great capacity to retain salt (Na+, Cl-) and to excrete potassium (K+) and an alkaline load (HCO3-), which was, until recently, in perfect adequacy with our food intake. However, in recent decades, our diet has changed dramatically. Thus, in addition to very high fat and sugar intake, it is characterized by a change in electrolyte intake due in particular to an excessive consumption of animal proteins and processed industrial foods causing an increase in the acid and sodium load and a drop in potassium intake. This so-called "western" or "modern" diet goes against what the kidneys are best suited for. However, they retain the ability to respond to this change by being able to retain K + and excrete large amounts of acid and salt. This ability is partly linked to the presence of a particular, infrequent cell type located in the distal part of the nephron, which is type A intercalated cells (ICA). Thus, the number of these cells increases in response to an acid load or a restriction in K+ and they are equipped with ion transporters allowing the excretion of acid and the retention of K+. More recently, we discovered that these cells also have the ability to secrete salt. Thus, ICAs seem to be the kidney cells that allow us to survive our Western diet every day. However, they have received relatively little attention compared to other kidney cells. The mechanisms that govern their ability to increase their numbers and stimulate their transport systems are still poorly understood.
In addition, in certain pathologies inducing electrolyte disturbances (of genetic origin or induced by drug treatment), ACIs and their regulation could play an important role.
We therefore propose a complete research project which will aim to characterize the mechanisms regulating ICA in the context of changes in ion intakes linked to the characteristics of the Western diet (rich in acid or rich in salt or poor in K+) and in the context of renal pathologies in order to better understand the role of these cells and their importance in renal function.
This project has three specific objectives: 1/ to understand the mechanisms of cellular plasticity of these cells and 2/ to identify and study the regulatory pathways that control the functions of these cells, and 3/ to establish the link between the effectors of these pathways and the electrolyte disorders observed in human pathologies.
To achieve this, we will implement experiments that involve cell biology and physiology approaches that are unique in France (measurements of ion transport systems on isolated renal tubules, monitoring of the fate of ICA in vivo by cell lineage, etc.) for which our consortium has mastered all the concepts since many years.