title: The potential contribution of circulating and locally produced leptin to cardiac hypertrophy and failure.
abstract: Leptin is a 16 kDa peptide that was first identified in 1994 through positional cloning of the mouse obesity gene. Although the primary function of leptin is to act a satiety factor through its actions on the hypothalamus, it is now widely recognized that leptin can exert effects on many other organs through activation of its receptors, which are ubiquitously expressed. Leptin is secreted primarily by white adipocytes, but it is also produced by other tissues including the heart where it can exert effects in an autocrine or paracrine manner. One of these effects involves the induction of cardiomyocyte hypertrophy, which appears to occur via multiple cell signalling mechanisms. As adipocytes are the primary site of leptin production, plasma leptin concentrations are generally positively related with body mass index and the degree of adiposity. However, hyperleptinemia is also associated with cardiovascular disease, including heart failure, in the absence of obesity. Here we review the potential role of leptin in heart disease, particularly pertaining to its potential contribution to myocardial remodelling and heart failure, as well as the underlying mechanisms. We further discuss potential interactions between leptin and another adipokine, adiponectin, and the potential implications of this interaction in terms of fully understanding leptin's effects.
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada.
authors.forename: Morris
authors.initials: M
authors.lastname: Karmazyn
authors.forename: Xiaohong Tracey
authors.initials: XT
authors.lastname: Gan
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Rajapurohitam
mesh_terms: D052242:Adiponectin / Q000502:physiology; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D001823:Body Composition / Q000502:physiology; D019703:Calcineurin / Q000502:physiology; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D008929:Mitochondria, Heart / Q000502:physiology; D019936:Probiotics; D011506:Proteins / Q000378:metabolism; D054411:Receptors, Leptin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D052242:Adiponectin; D020738:Leptin; D011506:Proteins; D054411:Receptors, Leptin; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D054460:rho-Associated Kinases; D019703:Calcineurin