Leptin Mediates the Increase in Blood Pressure Associated with Obesity

Stephanie Simonds; Jack Pryor; Eric Ravussin; Frank Greenway; Ralph Dileone; Andrew Allen; Jaspreet Bassi; Joel Elmquist; Julia Keogh; Elana Henning; Martin Myers Jr; Julio Licinio; Russell Brown; Pablo Enriori; Stephen O'Rahilly; Scott Sternson; Kevin Grove; David Spanswick; Sadaf Farooqi; Michael Cowley

doi:10.1016/j.cell.2014.10.058

Leptin Mediates the Increase in Blood Pressure Associated with Obesity

Stephanie Simonds, Jack Pryor, Eric Ravussin, Frank Greenway, Ralph Dileone, Andrew Allen, Jaspreet Bassi, Joel Elmquist, Julia Keogh, Elana Henning, Martin Myers Jr, Julio Licinio, Russell Brown, Pablo Enriori, Stephen O'Rahilly, Scott Sternson, Kevin Grove, David Spanswick, Sadaf Farooqi, Michael Cowley

Research output: Contribution to journal › Article › peer-review

246 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1404-1416
Number of pages	13
Journal	Cell
Volume	159
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2014.10.058
Publication status	Published - 4 Dec 2014

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Simonds, S., Pryor, J., Ravussin, E., Greenway, F., Dileone, R., Allen, A., Bassi, J., Elmquist, J., Keogh, J., Henning, E., Myers Jr, M., Licinio, J., Brown, R., Enriori, P., O'Rahilly, S., Sternson, S., Grove, K., Spanswick, D., Farooqi, S., & Cowley, M. (2014). Leptin Mediates the Increase in Blood Pressure Associated with Obesity. Cell, 159(6), 1404-1416. https://doi.org/10.1016/j.cell.2014.10.058

@article{7354d6ff205840fa97a1e57bb1ba2078,

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.",

author = "Stephanie Simonds and Jack Pryor and Eric Ravussin and Frank Greenway and Ralph Dileone and Andrew Allen and Jaspreet Bassi and Joel Elmquist and Julia Keogh and Elana Henning and {Myers Jr}, Martin and Julio Licinio and Russell Brown and Pablo Enriori and Stephen O'Rahilly and Scott Sternson and Kevin Grove and David Spanswick and Sadaf Farooqi and Michael Cowley",

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Simonds, S, Pryor, J, Ravussin, E, Greenway, F, Dileone, R, Allen, A, Bassi, J, Elmquist, J, Keogh, J, Henning, E, Myers Jr, M, Licinio, J, Brown, R, Enriori, P, O'Rahilly, S, Sternson, S, Grove, K, Spanswick, D, Farooqi, S & Cowley, M 2014, 'Leptin Mediates the Increase in Blood Pressure Associated with Obesity', Cell, vol. 159, no. 6, pp. 1404-1416. https://doi.org/10.1016/j.cell.2014.10.058

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AU - Simonds, Stephanie

AU - Pryor, Jack

AU - Ravussin, Eric

AU - Greenway, Frank

AU - Dileone, Ralph

AU - Allen, Andrew

AU - Bassi, Jaspreet

AU - Elmquist, Joel

AU - Keogh, Julia

AU - Henning, Elana

AU - Myers Jr, Martin

AU - Licinio, Julio

AU - Brown, Russell

AU - Enriori, Pablo

AU - O'Rahilly, Stephen

AU - Sternson, Scott

AU - Grove, Kevin

AU - Spanswick, David

AU - Farooqi, Sadaf

AU - Cowley, Michael

PY - 2014/12/4

Y1 - 2014/12/4

N2 - 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.

AB - 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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JO - Cell

JF - Cell

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Leptin Mediates the Increase in Blood Pressure Associated with Obesity

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