Journal article
Leptin mediates the increase in blood pressure associated with obesity
SE Simonds, JT Pryor, E Ravussin, FL Greenway, R Dileone, AM Allen, J Bassi, JK Elmquist, JM Keogh, E Henning, MG Myers, J Licinio, RD Brown, PJ Enriori, S O'Rahilly, SM Sternson, KL Grove, DC Spanswick, IS Farooqi, MA Cowley
Cell | Published : 2014
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, in..
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Awarded by Leverhulme Trust
Funding Acknowledgements
This work was supported by the Heart Foundation of Australia (M.A.C. and S.E.S.), the National Health and Medical Research Council of Australia (1029188 to M.A.C. and 1063955 to D.C.S.), Monash University (S.E.S.), Pfizer Australia (M.A.C.), a NORC Center grant (P30DK072476) at the Pennington Biomedical Research Center (E.R., F.L.G., and J.L.), the Leverhulme Trust (J.T.P.), the Wellcome Trust (082390/Z/07/Z) (I.S.F.), Medical Research Council (I.S.F.), NIHR Cambridge Biomedical Research Centre (I.S.F. and S.O.R.), and the Bernard Wolfe Health Neuroscience Fund (I.S.F.). We thank Professor Streamson Chua for the LepR flox mice. J.L. and I.S.F. treat patients with recombinant human leptin which is provided by BMS/AstraZeneca.