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

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172 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 languageEnglish
Pages (from-to)1404 - 1416
Number of pages13
JournalCell
Volume159
Issue number6
DOIs
Publication statusPublished - 2014

Cite this

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