The University of Hyderabad (UoH)-National Institute of Nutrition (NIN) team investigated the mechanism of Obesity-induced Proteinuria
Research led by City Scientists, Dr. Anil Kumar Pasupulati (Associate Professor, University of Hyderabad) and Dr. G. Bhanuprakash Reddy (Scientist G, NIN) investigated the pathobiology of obesity-induced kidney ailments. Obesity is a pandemic, and it is a disease of the modern world. People with obesity suffer from several complications, including kidney injury, which is manifested by proteinuria. These two scientists unraveled the cellular and molecular basis for obesity-related proteinuria using the Wistar NIN-Obese rat model and a high-fat (40%) fed mice model. In their studies, they found that both models of obesity have severe proteinuria. Upon investigation, they found that podocytes, crucial cells in the nephron (the functional unit of the kidney), are injured, i.e., they showed cellular distortions.
Developmental Origins of Obesity Kidney Disease
Further, they found that the WT1 (Wilms Tumor1) transcription factor gets up-regulated in podocytes from obese rats and high-fat-fed mice. Interestingly, WT1 is essential in kidney development in the embryonic stages, and in adults, its expression is minimal and confined only to podocytes. These scientists observed reactivation of WT1 in obese rodent models, which is concurrent with increased mobility of otherwise static podocytes. They believe that reactivation of the embryologically active transcription factor, WT1, could be the basis for observed podocyte damage and proteinuria in obese-rodent models. Big-data analysis from patients with chronic kidney disease revealed elevated WT1 expression in podocytes and their precursors.
P Anil Kumar
G. Bhanuprakash Reddy
Currently, both groups are intensively investigating means to curtail WT1 in obese settings to prevent obesity-induced podocyte injury and, in turn, to control proteinuria. These scientists thank their lab members Sneha Jakotia (NIN) and Rajesh Kavvuri (UoH), who significantly contributed to the study. The Science and Engineering Research Board (SERB), India, funded this study.
This study was published recently in “International Journal of Obesity”, a Nature Press Journal.