Obesity is a pandemic and a disease of the modern world. People with obesity suffer from several complications, including kidney injury, which is manifested by ‘proteinuria’. It is elevated protein in the urine which could be a sign of kidney disease.
The prevalence of obesity is increasing worldwide at an alarming rate along with the incidence of cardiovascular and metabolic diseases. Obesity is also the most potent risk factor for developing Chronic Kidney Disease (CKD) though precise mechanisms underlying the association between obesity and CKD remain unexplored. Now, research led by UoH associate professor, Department of Biochemistry, School of Life Sciences Anil Kumar Pasupulati and ICMR-National Institute of Nutrition (NIN) scientist G. Bhanuprakash Reddy has investigated the patho-biology of obesity-induced kidney ailments.
The scientists had unravelled the cellular and molecular basis for obesity-related proteinuria using the ‘Wistar NIN-Obese rat model’ and a high-fat (40%) fed mice model. Kidney functional parameters, micro-anatomical manifestations, and morphology were investigated in both experimental animal models. Gene expression analysis in the rodents was compared with human subjects by data mining using ‘Nephroseq’ and ‘Kidney Precision Medicine Project’ database. In their studies, they found that both models of obesity have severe proteinuria where ‘podocytes’ or the crucial cells in the functional unit of the kidney – nephron, are injured as they showed cellular distortions. Further, they also found that the WT1 (Wilms Tumor1) transcription factor gets up-regulated in obese rats and high-fat-fed mice. While WT1 is essential in kidney development in the embryonic stages, in adults, its expression is minimal.
Hence, scientists observed that the reactivation of WT1 in obese rodent models could be the basis for nephron cell damage and proteinuria in obese-rodent models. Big-data analysis from patients with chronic kidney disease also revealed elevated WT1 expression in nephron cells.
Currently, the scientists are intensively investigating means to curtail WT1 in obese settings to prevent obesity-induced kidney injury and, in turn, to control proteinuria. Lab members Sneha Jakotia (NIN) and Rajesh Kavvuri (UoH), had also contributed to the study funded by the Science and Engineering Research Board (SERB), said a press release on Thursday.
