pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57BI6 and ApoE Knockout Mice Fed a Western Diet

Authors

Komal Sodhi
K Srikanthan
P Goguet-Rubio
A Nichols
A Mallick
A Nawab
R Martin
P Shah
M ChaudhryFollow
S Sigdel
M El-Hamdani
J LiuFollow
Z Xie
Nader Abraham, New York Medical CollegeFollow
J Shapiro

DOI

10.1038/s41598-017-00306-5

Journal Title

Scientific Reports

First Page

193

Document Type

Article

Publication Date

3-1-2017

Department

Medicine

Abstract

We have previously reported that the alpha1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity, but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. And furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype.

Recommended Citation

Sodhi, K., Srikanthan, K., Goguet-Rubio, P., Nichols, A., Mallick, A., Nawab, A., Martin, R., Shah, P., Chaudhry, M., Sigdel, S., El-Hamdani, M., Liu, J., Xie, Z., Abraham, N., & Shapiro, J. (2017). pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57BI6 and ApoE Knockout Mice Fed a Western Diet. Scientific Reports, 7 (1), 193. https://doi.org/10.1038/s41598-017-00306-5

Publisher's Statement

Originally published in Scientific Reports volume 7, Article number: 193 (2017). The original material can be found here.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.