title: Identification of functional leptin receptors expressed in ventricular mitochondria.
abstract: Leptin is a 16 kDa pro-satiety peptide produced primarily not only by white adipocytes but also by numerous other tissues including the heart. Circulating leptin exerts its effect through specific receptors, although its principle actions are dependent on the activation of the long form of the leptin receptor, termed OBRb. As leptin is also produced within the cardiomyocyte, we hypothesized that the peptide can also exert effects by targeting intracellular sites. Accordingly, we determined whether cardiac mitochondria express functional leptin receptors. The presence of mitochondrial OBRb was identified through Western blotting of isolated mitochondria, immunofluorescence as well as immunogold labeling with electron microscopy. Although leptin had no direct effect on mitochondrial integrity, it profoundly enhanced the ability of calcium to induce mitochondrial swelling, an effect partially reversed by an OBR antagonist. 24 h exposure to leptin (50 ng/ml) was without effect on mitochondria in cultured neonatal rat ventricular myocytes in contrast to leptin tagged with a 10 amino acid membrane translocation sequence which significantly induced mitochondrial permeability transition pore opening, whereas both leptins produced a hypertrophic response. Our results therefore show that mitochondria express functional OBR which may be of importance toward understanding the role of intracellularly derived leptin in cardiac physiology and pathology.
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, London, ON, N6A 5C1, Canada.|Division Academica Multidisciplinaria de Comalcalco, Universidad Juarez Autonoma de Tabasco, Tabasco, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martinez-Abundis
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, London, ON, N6A 5C1, Canada.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Rajapurohitam
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, London, ON, N6A 5C1, Canada. morris.karmazyn@schulich.uwo.ca.
authors.forename: Morris
authors.initials: M
authors.lastname: Karmazyn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D054411:Receptors, Leptin / Q000378:metabolism*
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D054411:Receptors, Leptin; D002118:Calcium
keywords: Heart; Mitochondria; Mitochondrial OBR expression; Mitochondrial swelling