Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury
Authors: Jianxin Sun
Nadan Wang
Benjamin T Suratt
Ying Zhu
Bishnuhari Paudyal
Dilip Shah
Michelle Duong
Ross Summer
Kenneth Walsh
Caleb B Kallen
Freddy Romero
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: Obesity; acute respiratory distress syndrome (ARDS); pulmonary circulation; chronic low grade inflammation; pulmonary vascular homeostasis
Affiliations: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA., Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA., Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA., Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA., 1] Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA [2] Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China., Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, 02118, USA.

Abstract:  Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans. 

Retracted: Yes

PubPeer comments:
 Figure 1e. Much more similar than expected. https: imgur.com baR0bAq , 
 Figure 4c. Much more similar than expected. https: imgur.com h6V3xQa , 
 Figure 5f. Much more similar than expected. https: imgur.com dbCajGt , 
 Figure 5f. Much more similar than expected. https: imgur.com U2hgbsp , 
 Figure 5f. Much more similar than expected. https: imgur.com r5QgsPN , 
 Figure 1c. Much more similar than expected. https: imgur.com cdLfbSa , 
 Figure 5e. Much more similar than expected. https: imgur.com 9ITTz2c , 
 In light of these serious concerns, could the authors please provide original uncropped scans here or provide a link to a public repository? , 
 All uncropped gels are being sent to the editorial board of this journal. Kind regards. , 
 #9 Status update? See also Supplemental Figure 1; a smear unexpectedly seems to appear in triplicate. *** False color ![file] *** ![file] , 
 See also Supplemental Figure 4. *** False color ![file] *** ![file] , 
 Supplementary figure 8. Much more similar and different than expected. Lanes p-Src panel very similar (inside red rectangles), yet accompanying beta-catenin lanes are different. ![file] , 
 #9 Dr. Summer: As the journal seems to be having difficulty reviewing the original scans, could you please post them here so the expert reviewers on PubPeer can aid the journal in their investigation? You may post a link here to an external site (such as Imgur.com or Google Drive) to provide readers access to larger original images. Thank you. , 
 Editorial notice of concern has been added to the paper:  15 September 2021 Editor s Note: Readers are alerted that the reliability of the western blot data reported in this article is currently under dispute. The Editorial team is currently investigating these concerns. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full. , 
 **Retracted**. February 3, 2022 u201cRetraction of: Scientific Reports https: doi.org 10.1038 srep11362, published online 12 June 2015 The Authors have retracted this Article. After publication of this Article, concerns have been raised about irregularities in the western blot data. In particular, the following bands appear to be duplicated: Fig. 1e HFD p-Src lane 1 and 3; Fig. 4c NCD Ve-cadherin lane 1 and 3 Fig. 5e HFD+u2009APN ICAM-1 lane 1 and 2 Fig. 5f HFD beta-catenin lane 2 and HFD+u2009APN beta-catenin lane 1 Fig. S1d HFD beta-catenin all lanes Fig. S4c NCD beta-catenin lane 1 and 3. Additionally, the beta-catenin subpanel in Fig. 5f was subsequently reused in another study [1] and described as showing GRP87. The Authors were unable to provide the original high resolution scanned images for these blots. Therefore, the validity of the presented results cannot be confirmed. Dilip Shah, Nadan Wang, Benjamin T. Suratt, Jianxin Sun, Ying Zhu, Kenneth Walsh and Ross Summer agree to this retraction. Freddy Romero, Bishnuhari Paudyal and Caleb B. Kallen have not responded to any correspondence from the editor or publisher about this retraction. The Publisher has not been able to obtain a current email address for Michelle Duong.u201d , 
 03 Feb 2022 Retraction. https: www.nature.com articles s41598-022-06475-2 Retraction of: Scientific Reports https: doi.org 10.1038 srep11362, published online 12 June 2015 The Authors have retracted this Article. After publication of this Article, concerns have been raised about irregularities in the western blot data. In particular, the following bands appear to be duplicated: Fig. 1e HFD p-Src lane 1 and 3; Fig. 4c NCD Ve-cadherin lane 1 and 3 Fig. 5e HFD+u2009APN ICAM-1 lane 1 and 2 Fig. 5f HFD beta-catenin lane 2 and HFD+u2009APN beta-catenin lane 1 Fig. S1d HFD beta-catenin all lanes Fig. S4c NCD beta-catenin lane 1 and 3. Additionally, the beta-catenin subpanel in Fig. 5f was subsequently reused in another study [1] and described as showing GRP87. The Authors were unable to provide the original high resolution scanned images for these blots. Therefore, the validity of the presented results cannot be confirmed. Dilip Shah, Nadan Wang, Benjamin T. Suratt, Jianxin Sun, Ying Zhu, Kenneth Walsh and Ross Summer agree to this retraction. Freddy Romero, Bishnuhari Paudyal and Caleb B. Kallen have not responded to any correspondence from the editor or publisher about this retraction. The Publisher has not been able to obtain a current email address for Michelle Duong. Reference 1. Shah, D. et al. Obesity-induced endoplasmic reticulum stress causes lung endothelial dysfunction and promotes acute lung injury. Am. J. Respir. Cell. Mol. Biol. 57, 204u2013215. https: doi.org 10.1165 rcmb.2016-0310OC (2017). , 
  This article was retracted on 03 February 2022  15 September 2021 Editor s Note: Readers are alerted that the reliability of the western blot data reported in this article is currently under dispute. The Editorial team is currently investigating these concerns. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full.  Additionally, the beta-catenin subpanel in Fig. 5f was subsequently reused in another study [1] and described as showing GRP87. The Authors were unable to provide the original high resolution scanned images for these blots. Therefore, the validity of the presented results cannot be confirmed. , 
 See also Retraction Watch coverage: https: retractionwatch.com 2022 02 08 philadelphia-area-lung-researcher-up-to-six-retractions ,