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Updated: Mar 29, 2026

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
RETRACTED: pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis
Komal Sodhi1, Kyle Maxwell1, Yanling Yan1
1Departments of Medicine, Pharmacology, and Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA.
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.
Insights
A novel peptide, pNaKtide, targeting the Na/K-ATPase pathway, effectively reduced obesity and improved insulin sensitivity in mice. This suggests inhibiting Na/K-ATPase amplification of oxidative stress may combat metabolic syndrome.
Area of Science:
- Biochemistry
- Physiology
- Metabolic Research
Background:
- Obesity is a global epidemic and a primary risk factor for metabolic syndrome.
- Oxidative stress contributes to obesity development and maintenance.
- Na/K-ATPase is identified as a pathway that amplifies oxidant signaling.
Purpose of the Study:
- To investigate if pNaKtide, an inhibitor of Na/K-ATPase, can ameliorate obesity phenotypes.
- To explore the potential of targeting Na/K-ATPase for treating obesity and related metabolic disorders.
Main Methods:
- In vitro studies using isolated murine preadipocytes (3T3L1 cells).
- In vivo studies using C57Bl6 mice fed a high-fat diet.
- Administration of pNaKtide to assess its effects on oxidative stress, lipid accumulation, body weight, redox balance, inflammation, and insulin sensitivity.
Main Results:
- pNaKtide dose-dependently attenuated oxidant stress and lipid accumulation in 3T3L1 cells.
- In mice, pNaKtide administration reduced body weight gain.
- pNaKtide restored systemic redox and inflammatory balance and improved insulin sensitivity.
Conclusions:
- Inhibition of Na/K-ATPase amplification of oxidative stress is a potential therapeutic strategy.
- pNaKtide demonstrates promise in combating obesity, insulin resistance, and metabolic syndrome.
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