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.
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Authors | Stephanie E Simonds, Jack T Pryor, Eric Ravussin, Frank L Greenway, Ralph Dileone, Andrew M Allen, Jaspreet Bassi, Joel K Elmquist, Julia M Keogh, Elana Henning, Martin G Myers Jr, Julio Licinio, Russell D Brown, Pablo J Enriori, Stephen O'Rahilly, Scott M Sternson, Kevin L Grove, David C Spanswick, I Sadaf Farooqi, Michael A Cowley |
Journal | Cell
(Cell)
Vol. 159
Issue 6
Pg. 1404-16
(Dec 04 2014)
ISSN: 1097-4172 [Electronic] United States |
PMID | 25480301
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Animals
- Hypertension
(metabolism)
- Leptin
(genetics, metabolism)
- Mice, Inbred C57BL
- Mutation
- Neurons
(metabolism)
- Obesity
(metabolism, pathology)
- Receptors, Leptin
(genetics, metabolism)
- Signal Transduction
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