Researchers with the Marshall University Joan C. Edwards School of Medicine and the Marshall University Institute for Interdisciplinary Research (MIIR) have identified a mechanism for blocking the signal by which the cellular sodium-potassium pump amplifies oxidants (reactive oxygen species). These oxidants lead to obesity and metabolic syndrome.
Their research, “pNaKtide Inhibits Na/K-ATPase Reactive Oxygen Species Amplification and Attenuates Adipogenesis,” was published today in the journal Science Advances.
Joseph I. Shapiro, M.D., dean of the school of medicine and the study’s senior author, says the study is a true collaborative effort.
“I am extremely proud of this work, as the studies were conceived of, performed and analyzed entirely at Marshall University,” Shapiro said. “This work was based on two important components. We employed a peptide, pNaKtide, which was derived from the novel hypothesis developed by Marshall’s MIIR director, Dr. Zijian Xie. Specifically, Dr. Xie has shown that in addition to its well-described role as an ion transporter, the sodium pump also regulates signal transduction and oxidant amplification. We also exploited work from Marshall’s SOM vice-dean for research, Dr. Nader Abraham, who has demonstrated a key role for oxidant stress in adipocytes in the development of obesity. The studies, which address a critical problem in the Appalachian population we serve, were performed entirely by our research staff at Marshall University.”
First author Komal Sodhi, M.D., assistant professor of surgery and pharmacology at Marshall, says the research examined a peptide (pNaKtide) designed to block the sodium potassium Na/K-ATPase signaling cascade, which altered the phenotype of adipocytes (fat cells) in a cell culture system.
“We found this decreased the development of obesity and metabolic syndrome in mice subjected to a high-fat diet, “Sodhi said. “The studies performed strongly supported this idea and suggest that if this is confirmed in humans, the Na/K-ATPase might ultimately be a therapeutic target for clinical conditions like obesity and metabolic syndrome, which are particularly relevant to West Virginia where more than a third of the population is currently obese.”
Shapiro said while there are years of work ahead for researchers to determine the impact on humans, they believe they have hit on a feasible strategy for treating obesity and metabolic syndrome.
“The bottom line is that we’ve identified a novel mechanism by which to address oxidant stress and, through this mechanism, treat obesity,” Shapiro said. “Our work opens up a new target for intervention in this disease as well as possibly other diseases characterized by oxidant stress.”
In addition to Shapiro and Sodhi, Marshall’s team of researchers includes Kyle Maxwell; Yanling Yan, Ph.D.; Jiang Liu, M.D., Ph.D.; Muhammad A. Chaudhry, M.A.; Morghan Getty; Zijian Xie, Ph.D.; and Nader G. Abraham, Ph.D.
Funding for this study was provided by the National Institutes of Health, BrickStreet Foundation, and the Huntington Foundation, Inc.
Marshall University Joan C. Edwards School of Medicine
The Joan C. Edwards School of Medicine is a community-based, Veterans Affairs-affiliated medical school dedicated to providing high-quality medical education and postgraduate training programs to foster a skilled physician workforce to meet the unique health care needs of West Virginia and Central Appalachia. The school seeks to develop centers of excellence in clinical care, including primary care in rural underserved areas, focused and responsive programs of biomedical science graduate study, biomedical and clinical science research, academic scholarship and public service outreach. For more information, visit www.musom.marshall.edu.
Marshall Institute for Interdisciplinary Research
MIIR is Marshall University’s key vehicle for advancing regional economic development. The institute’s scientists are developing a focused program of biotechnology research dedicated to exploring new treatments for cancer and heart and kidney disease, producing patentable scientific breakthroughs and creating new businesses based on those discoveries. Learn more at http://www.marshall.edu/miir.