Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications.
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.
Hypertension 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. allyn-mark@uiowa.edu
Allyn L
AL
Mark
Marcelo L G
ML
Correia
Kamal
K
Rahmouni
William G
WG
Haynes
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D004351:Drug Resistance / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D009765:Obesity / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
D020738:Leptin