Leptin mediates the increase in blood pressure associated with obesity
Authors: Jack T Pryor
Julio Licinio
Stephen O&#x27;Rahilly
Stephanie E Simonds
Russell D Brown
Pablo J Enriori
Scott M Sternson
Martin G Myers Jr
Michael A Cowley
Frank L Greenway
Andrew M Allen
David C Spanswick
Joel K Elmquist
Jaspreet Bassi
Julia M Keogh
I Sadaf Farooqi
Kevin L Grove
Eric Ravussin
Elana Henning
Ralph Dileone
Journal: Cell (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Obesity; Blood pressure; Leptin; Leptin receptors; Cardiovascular diseases
Affiliations: Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia., Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Neurosolutions Ltd., Coventry CV4 7ZS, UK., The Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA., Department of Psychiatry, Yale School of Medicine, New Haven, CT 06511, USA., Department of Physiology, The University of Melbourne, Victoria 3010, Australia., Division of Endocrinology & Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX¬†75390, USA., University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK., Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA., Mind and Brain Theme, South Australian Health and Medical Research Institute and Department of Psychiatry, School of Medicine, Flinders¬†University, Adelaide, SA 5001, Australia., Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA., Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Portland, OR 97239, USA., Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK., University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: ., Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address: .

Abstract:  Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with loss-of-function mutations in leptin and the LepR have low BP despite severe obesity. Leptin's effects on BP are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), as blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH caused a rapid reduction of BP in DIO mice, independent of changes in weight. Re-expression of LepRs in the DMH of DIO LepR-deficient mice caused an increase in BP. These studies demonstrate that leptin couples changes in weight to changes in BP in mammalian species. 

Retracted: No

PubPeer comments:
 The same brain seems to have been reused for between Figure 1C and Figure 2C (please see marked brains in the attached image). In figure 2C, an image of ventricular sections was added to the panel. Could the authors please comment on the design of mouse experiments?  , 
 Dear Hedyotis Flavescens, Thank you so much for reminding us the potential misleading in the figures. The experimental animals were divided into four groups including nonDM-sham, nonDM-stroke, DM-sham and DM-stroke group. Figure 1 shows the difference between sham- and stroke- nonDM mice, that is, the labeling in Fig1 C  stroke group is the  nonDM stroke group . The purpose of Fig.1 is to compare the effect of sham- and stroke- induced injury in the brain, for this reason, we didn t label  nonDM for the stroke panel. We think that is what might cause the misunderstanding. The images shown in figure 1C and figure 2C are the same mouse brain from non-DM stroke group, which represents the same degree of the injury of the brain tissue. We didn t intend to use the duplicated image to show difference between groups, we just want to show the same degree of the injuries induced by the same treatment, hence the same image of nonDM-stroke brain was used. However, we didn t expect that will cause concerns. We agree that it is better to use different images in the same paper, to avoid misleading. We apologize for the potential misunderstanding. For this reason, we have contacted the editor of the journal and ask for a correction for the representative images of the mouse model. We really appreciate your attention on our publication, as well as pointing out the potential misleading. ,