The Adipocyte Na/K-ATPase Oxidant Amplification Loop is the Central Regulator of Western Diet-Induced Obesity and Associated Comorbidities
Authors: Niharika N Bhardwaj
Zijian Xie
Cameron Cottrill
Rebecca D Pratt
Brian Snoad
Joseph I Shapiro
Nader G Abraham
Komal Sodhi
Austin Jelcick
Brandon Henderson
Jiang Liu
Juan R Sanabria
Cameron Brickman
Athar Nawab
Hari Vishal Lakhani
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: Obesity; pNaKtide; Na/K-ATPase; adipocytes; western diet
Affiliations: Departments of Medicine, Surgery, Biomedical Sciences, and Healthcare Informatics Program, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA., Vector Builder Incorporated, Shenandoah, TX, 77384, USA., Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA., Departments of Medicine, Surgery, Biomedical Sciences, and Healthcare Informatics Program, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA. .

Abstract:  Obesity has become a worldwide epidemic. We have previously reported that systemic administration of pNaKtide which targets the Na/K-ATPase oxidant amplification loop (NKAL) was able to decrease systemic oxidative stress and adiposity in mice fed a high fat and fructose supplemented western diet (WD). As adipocytes are believed to play a central role in the development of obesity and its related comorbidities, we examined whether lentiviral-mediated adipocyte-specific expression of NaKtide, a peptide derived from the N domain of the alpha1 Na/K-ATPase subunit, could ameliorate the effects of the WD. C57BL6 mice were fed a WD, which activated Na/K-ATPase signaling in the adipocytes and induced an obese phenotype and caused an increase in plasma levels of leptin, IL-6 and TNFŒ±. WD also decreased locomotor activity, expression of the D2 receptor and tyrosine hydroxylase in brain tissue, while markers of neurodegeneration and neuronal apoptosis were increased following the WD. Selective adipocyte expression of NaKtide in these mice fed a WD attenuated all of these changes including the brain biochemical alterations and behavioral adaptations. These data suggest that adipocyte derived cytokines play an essential role in the development of obesity induced by a WD and that targeting the adipocyte NKAL loop may serve as an effective therapeutic strategy. 

Retracted: No

PubPeer comments:
 Figure 4C. Much more similar than expected. https: imgur.com a eR8oygB , 
 Retraction of: Scientific Reports https: doi.org 10.1038 s41598-019-44350-9, published online 28 May 2019 Retraction Note: The Adipocyte Na K-ATPase Oxidant Amplification Loop is the Central Regulator of Western Diet-Induced Obesity and Associated Comorbidities The Editors have retracted this Article. After publication, concerns were raised regarding high similarity among different lanes in the Coomassie blue staining image in Fig. 4d. Further investigation has found that there are inconsistencies in the blot backgrounds in Figs. S5d, g and f, and S6b, d and f, which undermine the integrity of these gels. Furthermore, in the raw data provided by the authors (links to depository in the Data Availability section), there are unexplained similarities between images representing brain tissue  control - no treatment and  wd - no treatment groups (dapi channel; rotated by 180 degrees), and between images of liver tissue u201cwd-lenti-adipo-naktideu201d and u201cwd-lenti-adipo-gfpu201d groups (dapi channel; gfp image appears to be stretched). The Editors therefore no longer have confidence in the presented data. Brandon Henderson, Juan R. Sanabria, and Nader G. Abraham agree to this retraction. Rebecca D. Pratt, Cameron Cottrill, Niharika N. Bhardwaj, Jiang Liu, Joseph I. Shapiro, and Komal Sodhi do not agree to this retraction. Cameron Brickman, Athar Nawab, Brian Snoad, Hari Vishal Lakhani, Austin Jelcick, and Zijian Xie have not responded to any correspondence from the Editors about this retraction. , 
 https: retractionwatch.com 2022 06 08 medical-school-dean-up-to-five-retractions https: forbetterscience.com 2021 04 13 the-intellectual-leaps-of-joe-shapiro ,