(2014) Leptin mediates the increase in blood pressure associated with obesity. Cell, Volume 159 (Number 6). pp. 1404-1416. doi:10.1016/j.cell.2014.10.058 ISSN 0092-8674.

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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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Obesity -- Treatment, Leptin, Blood pressure
Journal or Publication Title:	Cell
Publisher:	Cell Press
ISSN:	0092-8674
Official Date:	4 December 2014
Dates:	Date Event 4 December 2014 Published 30 October 2014 Accepted 31 August 2014 Modified 27 May 2014 Submitted
Volume:	Volume 159
Number:	Number 6
Page Range:	pp. 1404-1416
DOI:	10.1016/j.cell.2014.10.058
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	28 December 2015
Date of first compliant Open Access:	28 December 2015
Funder:	National Heart Foundation of Australia (NHFA), National Health and Medical Research Council (Australia) (NHMRC) , Monash University, Pfizer Inc., NORC (Organization), Pennington Biomedical Research Center (PBRC), Leverhulme Trust (LT), Wellcome Trust (London, England), Medical Research Council (Great Britain) (MRC), National Institute for Health Research (Great Britain) (NIHR), Bernard Wolfe Health Neuroscience Fund (BFHNF)
Grant number:	1029188 (NHMRC), 1063955 (NHMRC)

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