title: Leptin mediates the increase in blood pressure associated with obesity.
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.
authors.affiliation: Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Simonds
authors.affiliation: Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Neurosolutions Ltd., Coventry CV4 7ZS, UK.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Pryor
authors.affiliation: The Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.affiliation: The Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Greenway
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT 06511, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Dileone
authors.affiliation: Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Allen
authors.affiliation: Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Bassi
authors.affiliation: Division of Endocrinology & Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Keogh
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Elana
authors.initials: E
authors.lastname: Henning
authors.affiliation: Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.affiliation: Mind and Brain Theme, South Australian Health and Medical Research Institute and Department of Psychiatry, School of Medicine, Flinders University, Adelaide, SA 5001, Australia.
authors.forename: Julio
authors.initials: J
authors.lastname: Licinio
authors.affiliation: Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Brown
authors.affiliation: Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Enriori
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.affiliation: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Sternson
authors.affiliation: Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Portland, OR 97239, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
authors.affiliation: Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Spanswick
authors.affiliation: 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.
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.affiliation: Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address: michael.cowley@monash.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
mesh_terms: D000818:Animals; D006973:Hypertension / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020738:Leptin; D054411:Receptors, Leptin