Leptin mediates the increase in blood pressure associated with obesity

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

doi:10.1016/j.cell.2014.10.058

Leptin mediates the increase in blood pressure associated with obesity

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

Physiology

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

270 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 - 2014

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2014.10.058

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Simonds, S. E., Pryor, J., Ravussin, E., Greenway, F. L., Dileone, R., Allen, A. M., Bassi, J. K., Elmquist, J. K., Keogh, J. M., Henning, E., Myers Jr, M. G., Licinio, J., Brown, R. D., Enriori, P., O'Rahilly, S., Sternson, S. M., Grove, K. L., Spanswick, D. C., Farooqi, I. S., & Cowley, M. A. (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{c47eedf723324039be34b902b9beba14,

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

year = "2014",

doi = "10.1016/j.cell.2014.10.058",

language = "English",

volume = "159",

pages = "1404 -- 1416",

journal = "Cell",

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publisher = "Cell Press",

number = "6",

}

Simonds, SE, Pryor, J, Ravussin, E, Greenway, FL, Dileone, R, Allen, AM, Bassi, JK, Elmquist, JK, Keogh, JM, Henning, E, Myers Jr, MG, Licinio, J, Brown, RD, Enriori, P, O'Rahilly, S, Sternson, SM, Grove, KL, Spanswick, DC, Farooqi, IS & Cowley, MA 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

TY - JOUR

T1 - Leptin mediates the increase in blood pressure associated with obesity

AU - Simonds, Stephanie Elise

AU - Pryor, Jack

AU - Ravussin, Eric

AU - Greenway, Frank L

AU - Dileone, Ralph

AU - Allen, Andrew Mark

AU - Bassi, Jaspreet K

AU - Elmquist, Joel K

AU - Keogh, Julia M

AU - Henning, Elana

AU - Myers Jr, Martin G

AU - Licinio, Julio

AU - Brown, Russell Deputy

AU - Enriori, Pablo

AU - O'Rahilly, Stephen

AU - Sternson, Scott M

AU - Grove, Kevin L

AU - Spanswick, David Charles

AU - Farooqi, I Sadaf

AU - Cowley, Michael Alexander

PY - 2014

Y1 - 2014

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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U2 - 10.1016/j.cell.2014.10.058

DO - 10.1016/j.cell.2014.10.058

M3 - Article

SN - 0092-8674

VL - 159

SP - 1404

EP - 1416

JO - Cell

JF - Cell

IS - 6

ER -

Leptin mediates the increase in blood pressure associated with obesity

Abstract

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Other files and links

Brain glucose-sensing: age- and energy-status-dependent plasticity of function-specific Pro-opiomelanocortin (POMC) glucose-sensing neurons in the arcuate nucleus of the hypothalamus

Can Blockade of Leptin Action in the Brain reduce Blood Pressure in Obese Mice?

Cite this

Leptin mediates the increase in blood pressure associated with obesity

Abstract

UN SDGs

Access to Document

Other files and links

Projects

Brain glucose-sensing: age- and energy-status-dependent plasticity of function-specific Pro-opiomelanocortin (POMC) glucose-sensing neurons in the arcuate nucleus of the hypothalamus

Can Blockade of Leptin Action in the Brain reduce Blood Pressure in Obese Mice?

Cite this