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Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications

Mark, Allyn L.a; Correia, Marcelo L. G.b; Rahmouni, Kamala; Haynes, William G.a

Review

Leptin, an adipocyte secreted hormone, acts in the hypothalamus to inhibit appetite and promote thermogenic metabolism, thereby reducing adiposity and body weight. Leptin has multiple autonomic and cardiovascular actions, including sympathetic activation, increases in endothelium derived nitric oxide (NO), and angiogenesis. The predominant cardiovascular effect of chronic hyperleptinemia is a pressor effect mediated by increased sympathetic activity. The sympathetic and cardiovascular actions of leptin are discussed and evidence derived from studies of obese mice for the novel concept of selective leptin resistance is reviewed. This concept holds that in some obese states, there is preservation of the sympathoexcitatory actions of leptin despite resistance to the satiety and weight-reducing actions of the hormone. Selective leptin resistance might explain how hyperleptinemia could contribute to increases in sympathetic activity and arterial pressure in obese states where there is resistance to the metabolic (satiety and weight-reducing) actions of leptin. It is speculated here, that this concept may have potential implications for human obesity, which is often associated with elevated plasma leptin and partial resistance to the satiety effects of leptin. If selective leptin resistance occurs in obese humans, then leptin could contribute to the sympathetic overactivity and hypertension despite resistance to its metabolic actions.

aHypertension Genetics Specialized Center of Research, the Department of Internal Medicine, University of Iowa College of Medicine and the Veterans Administration Medical Center, Iowa City, Iowa, USA. bPresent address: Hospital Universitario Pedtro Ernesto, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, sala 329, Rio de Janeiro, Brazil, CEP 20551–030.

Sponsorship: This work was supported by Hypertension Genetics Specialized Center of Research (HL44546) from the National Heart, Lung, and Blood Institute and by research funds from the Department of Veterans Affairs. L.G.C. was supported in part by the State University of Rio de Janeiro, Brazil. K.R. is supported by a postdoctoral fellowship award from the Heartland Affiliate of the American Heart Association (Number 0120606Z). W.G.H. is the recipient of the Pharmaceutical Research Manufacturers of America Faculty Development Award.

Correspondence and requests for reprints to Allyn L. Mark, 218 CMAB, College of Medicine, University of Iowa, Iowa City, Iowa, 52242–1101 USA. Tel: +1 319 353 5676; fax: +1 319 335 8318; e-mail: allyn-mark@uiowa.edu

Received 4 December 2001

Revised 24 March 2002

Accepted 2 April 2002

© 2002 Lippincott Williams & Wilkins, Inc.