Leptin mediates the increase in blood pressure associated with obesity.
View / Open Files
Authors
Simonds, Stephanie E
Pryor, Jack T
Ravussin, Eric
Greenway, Frank L
Dileone, Ralph
Allen, Andrew M
Bassi, Jaspreet
Elmquist, Joel K
Myers, Martin G
Licinio, Julio
Brown, Russell D
Enriori, Pablo J
Sternson, Scott M
Grove, Kevin L
Spanswick, David C
Cowley, Michael A
Publication Date
2014-12-04Journal Title
Cell
ISSN
0092-8674
Publisher
Elsevier BV
Volume
159
Issue
6
Pages
1404-1416
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
Simonds, S. E., Pryor, J. T., Ravussin, E., Greenway, F. L., Dileone, R., Allen, A. M., Bassi, J., et al. (2014). Leptin mediates the increase in blood pressure associated with obesity.. Cell, 159 (6), 1404-1416. https://doi.org/10.1016/j.cell.2014.10.058
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.
Keywords
Neurons, Animals, Mice, Inbred C57BL, Hypertension, Obesity, Leptin, Signal Transduction, Mutation, Receptors, Leptin
Sponsorship
Wellcome Trust (082390/Z/07/Z)
Medical Research Council (MC_UU_12012/1)
Medical Research Council (G0600717)
Medical Research Council (MC_UU_12012/5/B)
Wellcome Trust (095515/Z/11/Z)
Wellcome Trust (098497/Z/12/Z)
Identifiers
External DOI: https://doi.org/10.1016/j.cell.2014.10.058
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277462
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The following licence files are associated with this item: