Research ArticleBIOCHEMISTRY

pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis

Science Advances  16 Oct 2015:
Vol. 1, no. 9, e1500781
DOI: 10.1126/sciadv.1500781

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Abstract

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed a high-fat diet corroborated our in vitro observations. Administration of pNaKtide in these mice reduced body weight gain, restored systemic redox and inflammatory milieu, and, crucially, improved insulin sensitivity. Thus, we propose that inhibition of Na/K-ATPase amplification of oxidative stress may ultimately be a novel way to combat obesity, insulin resistance, and metabolic syndrome.

Keywords
  • pNaKtide peptide
  • Na/K-ATPase
  • oxidative stress
  • adipogenesis
  • metabolic syndrome
  • high-fat diet

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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