Inhibiting Ion Pump May Prevent Non-Alcoholic Fatty Liver Disease, Mouse Study Shows

Inhibiting Ion Pump May Prevent Non-Alcoholic Fatty Liver Disease, Mouse Study Shows

A peptide called pNaKtide has shown promise in improving the clinical manifestations associated with non-alcoholic fatty liver disease (NAFLD) and atherosclerosis, according to researchers at Marshall University’s Joan C. Edwards School of Medicine in Huntington, West Virginia.

If their findings are confirmed in patients, pNaKtide may become a reliable strategy to stop certain mechanisms underlying liver disease.

The study, “pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet.” appeared in Scientific Reports.

The team, led by Joseph Shapiro, MD, had previously shown that a protein called Na+/K+-ATPase contributes to the development of steatohepatitis, a form of hepatitis characterized by an accumulation of fat. The Na+/K+-ATPase works as a pump, controlling the levels of sodium (Na+) and potassium (K+) in the mitochondria, the cell’s compartment for energy production.

Researchers hypothesized that blocking this protein with pNaKtide could potentially improve some of the manifestations associated with an experimental model of NAFLD. Feeding two strains of mice a “Western” diet containing fat and fructose, researchers observed that treatment with pNaKtide reduced obesity, hepatic steatosis, inflammation and fibrosis. It also improved insulin sensitivity, dyslipidemia (abnormal levels of fat) and aorta damage in these animals.

Mice lacking the ApoE gene, which quickly develop atherosclerosis, also showed significant improvements upon treatment with pNaKtide.

“Our results showed that pNaKtide was very effective at ameliorating the development of NAFLD and atherosclerosis associated with this Western diet,” Shapiro said in a news release. “If this agent can ultimately be developed into a medication, it may have substantial utility on disease processes endemic to this region.”

Added the study’s first author, Komal Sodhi, MD: “Collectively, our study demonstrates [that the molecular pathways] controlled by the sodium-potassium pump significantly contributes to the development and progression of NAFLD and atherosclerosis. With these findings, we can better understand ways to treat or even prevent these conditions from occurring.”

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