Leptin mediates the increase in blood pressure associated with obesity

Stephanie E. Simonds, Jack T. Pryor, Eric Ravussin, Frank L. Greenway, Ralph Dileone, Andrew M. Allen, Jaspreet Bassi, Joel K. Elmquist, Julia M. Keogh, Elana Henning, Martin G. Myers, Julio Licinio, Russell D. Brown, Pablo J. Enriori, Stephen O'Rahilly, Scott M. Sternson, Kevin L. Grove, David C. Spanswick, I. Sadaf Farooqi, Michael A. Cowley

Research output: Contribution to journalArticle

153 Scopus citations

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 (US)
Pages (from-to)1404-1416
Number of pages13
JournalCell
Volume159
Issue number6
DOIs
Publication statusPublished - Dec 4 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Simonds, S. E., Pryor, J. T., Ravussin, E., Greenway, F. L., Dileone, R., Allen, A. M., ... 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