title: Leptin and the regulation of endothelial function in physiological and pathological conditions.
abstract: Obesity and the accompanying metabolic syndrome are among the most important causes of cardiovascular pathologies associated with endothelial dysfunction, such as arterial hypertension and atherosclerosis. This detrimental effect of obesity is mediated, in part, by excessive production of the adipose tissue hormone leptin. Under physiological conditions leptin induces endothelium-dependent vasorelaxation by stimulating nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Leptin activates endothelial NO synthase (eNOS) through a mechanism involving AMP-activated protein kinase (AMPK) and protein kinase B/Akt, which phosphorylates eNOS at Ser(1177) , increasing its activity. Under pathological conditions, such as obesity and metabolic syndrome, the NO-mediated vasodilatory effect of leptin is impaired. Resistance to the acute NO-mimetic effect of leptin is accounted for by chronic hyperleptinaemia and may result from different mechanisms, such as downregulation of leptin receptors, increased levels of circulating C-reactive protein, oxidative stress and overexpression of suppressor of cytokine signalling-3. In short-lasting obesity, impaired leptin-induced NO production is compensated by EDHF; however, in advanced metabolic syndrome, the contribution of EDHF to the haemodynamic effect of leptin becomes inefficient. Resistance to the vasodilatory effects of leptin may contribute to the development of arterial hypertension owing to unopposed stimulation of the sympathetic nervous system by this hormone.
authors.affiliation: Department of Pathophysiology, Medical University, Lublin, Poland. jerzy.beltowski@umlub.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bełtowski
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D020738:Leptin / Q000502:physiology*; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D014664:Vasodilation
chemical_list: D020738:Leptin