title: Selective leptin resistance revisited.
abstract: In addition to effects on appetite and metabolism, leptin influences many neuroendocrine and physiological systems, including the sympathetic nervous system. Building on my Carl Ludwig Lecture of the American Physiological Society, I review the sympathetic and cardiovascular actions of leptin. The review focuses on a critical analysis of the concept of selective leptin resistance (SLR) and the role of leptin in the pathogenesis of obesity-induced hypertension in both experimental animals and humans. We introduced the concept of SLR in 2002 to explain how leptin might increase blood pressure (BP) in obese states, such as diet-induced obesity (DIO), that are accompanied by partial leptin resistance. This concept, analogous to selective insulin resistance in the metabolic syndrome, holds that in several genetic and acquired models of obesity, there is preservation of the renal sympathetic and pressor actions of leptin despite attenuation of the appetite and weight-reducing actions. Two potential overlapping mechanisms of SLR are reviewed: 1) differential leptin molecular signaling pathways that mediate selective as opposed to universal leptin action and 2) brain site-specific leptin action and resistance. Although the phenomenon of SLR in DIO has so far focused on preservation of sympathetic and BP actions of leptin, consideration should be given to the possibility that this concept may extend to preservation of other actions of leptin. Finally, I review perplexing data on the effects of leptin on sympathetic activity and BP in humans and its role in human obesity-induced hypertension.
authors.affiliation: Department of Internal Medicine and the Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Allyn L
authors.initials: AL
authors.lastname: Mark
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D020738:Leptin
keywords: adipose tissue; blood pressure; renal; renin-angiotensin system; sympathetic