Study of Fat Cells May Hint at Target in Chronic Renal Failure

July 1, 2020

Previously, fat cells, called adipocytes, were not known to have a role in renal failure-associated cardiomyopathy.

Research that examined the role of fat cells in renal failure—associated cardiomyopathy may point to a new target in treating chronic renal failure, according to new findings.

A team from Marshall University’s Joan C. Edwards School of Medicine, publishing in the Journal of the American Society of Nephrology, used a mouse model to show a high fat diet interfered with the functioning of an enzyme responsible for transferring sodium outside of cells. Called Na/K-ATPase, it also prevents the development of renal failure-associated cardiomyopathy, as well as other features of renal failure, such as anemia.

Previously, fat cells, called adipocytes, were not known to have a role in renal failure—associated cardiomyopathy. But the experiment by the Marshall team showed that when mice were fed a diet designed to resemble a Western diet—high in fat and fructose—that caused the production of a peptide, NaKtide, in fat cells, which blocked the signaling function of Na/K-ATPase, which is known as the cells’ sodium pump. This pump mechanism moves sodium and potassium ions in an out of the cell and helps control cell volume.

However, when researchers targeted NaKtide production to skeletal muscle cells in the mice instead of fat cells, the process did not have a similar effect on cardiomyopathy or anemia.

"This research provides an important breakthrough with translational application and demonstrates that Na/K-ATPase oxidant-amplification loop and/or adipocytes are potential targets for disease intervention," lead author Komal Sodhi, MD, who is associate professor of surgery and biomedical sciences at the medical school, said in a statement.

If later studies can confirm this mechanism in humans, it could represent a new way therapeutic target in treating chronic renal failure.

"According to this novel study, targeting this oxidant amplification loop in adipocytes could serve as a viable clinical strategy for the prevention and treatment of renal failure-associated cardiomyopathy," said Joseph I. Shapiro, MD, dean of the Joan C. Edwards School of Medicine and the study's senior author.

Reference

Sodhi K, Wang X, Chaudry MA, et al. Central role for adipocyte Na,K-ATPase oxidant amplification loop in the pathogenesis of experimental uremic cardiomyopathy [published online June 25, 2020]. JASN. DOI: 10.1681/ASN.2019101070