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Leptin, the Autonomic Nervous System, and Hypertension

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Leptin

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Abstract

Although the importance of leptin in regulating energy balance and adiposity has been recognized since its discovery 20 years ago, there is considerable evidence that leptin may also play a key role in linking obesity with increased sympathetic nervous system (SNS) activity and hypertension. Leptin crosses the blood–brain barrier and activates multiple brain centers that control SNS activity and blood pressure (BP) mainly by activation of central nervous system (CNS) melanocortins. Deletion of leptin receptors specifically in proopiomelanocortin (POMC) neurons abolishes leptin’s effects to increase BP and renal sympathetic nervous system (SNS) activity, a key mediator of long-term BP regulation, but does not greatly attenuate leptin’s effects on appetite or energy expenditure. Also, genetic deficiency or pharmacological blockade of melanocortin 4 receptors (MC4R) in the CNS prevents leptin-induced increases in renal SNS activity and BP as well as obesity-induced hypertension. The crosstalk between peripheral signals (e.g. leptin) and activation of CNS pathways (e.g. the POMC-MC4R axis) in key hypothalamic and brainstem areas that regulate energy balance, SNS activity, and BP represents a potential target for treating obesity and its metabolic and cardiovascular consequences.

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Sources of Funding 

The authors’ research was supported by grants from the National Heart, Lung and Blood Institute (PO1 HL51971), the National Institute of General Medical Sciences (P20 GM104357), and by an American Heart Association Scientist Development Grant to Jussara M. do Carmo.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    Alexandre A. da Silva Ph.D.

  2. Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA

    Jussara M. do Carmo Ph.D., Zhen Wang Ph.D. & John E. Hall Ph.D.

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  1. Alexandre A. da Silva Ph.D.
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  2. Jussara M. do Carmo Ph.D.
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  3. Zhen Wang Ph.D.
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Correspondence to Alexandre A. da Silva Ph.D. .

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  1. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Sam Dagogo-Jack, MD

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da Silva, A.A., do Carmo, J.M., Wang, Z., Hall, J.E. (2015). Leptin, the Autonomic Nervous System, and Hypertension. In: Dagogo-Jack, MD, S. (eds) Leptin. Springer, Cham. https://doi.org/10.1007/978-3-319-09915-6_14

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