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Cell. 2014 Dec 4;159(6):1404-16. doi: 10.1016/j.cell.2014.10.058.

Leptin mediates the increase in blood pressure associated with obesity.

Author information

1
Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia.
2
Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Neurosolutions Ltd., Coventry CV4 7ZS, UK.
3
The Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
4
Department of Psychiatry, Yale School of Medicine, New Haven, CT 06511, USA.
5
Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
6
Division of Endocrinology & Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
7
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
8
Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
9
Mind and Brain Theme, South Australian Health and Medical Research Institute and Department of Psychiatry, School of Medicine, Flinders University, Adelaide, SA 5001, Australia.
10
Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
11
Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Portland, OR 97239, USA.
12
Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
13
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: isf20@cam.ac.uk.
14
Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address: michael.cowley@monash.edu.

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.

PMID:
25480301
PMCID:
PMC4259491
DOI:
10.1016/j.cell.2014.10.058
[Indexed for MEDLINE]
Free PMC Article

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