title: Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.
abstract: Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Blanca
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.
authors.forename: María V
authors.initials: MV
authors.lastname: Ruiz-Armenta
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zambrano
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.|Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, 8330024, Chile.
authors.forename: Rocío
authors.initials: R
authors.lastname: Salsoso
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Miguel-Carrasco
authors.affiliation: Program of Cardiovascular Diseases, Center for Applied Medical Research, University of Navarra, Avda. Pío XII 55, Pamplona, 31008, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuño
authors.affiliation: Facultad de Farmacia, Departamento de Bioquímica, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Revilla
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Avda. Manuel Siurot s/n, Sevilla, 41013, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.affiliation: Facultad de Farmacia, Departamento de Fisiología, Universidad de Sevilla, CL Profesor García González 2, Sevilla, 41012, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Avda. Manuel Siurot s/n, Sevilla, 41013, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002331:Carnitine / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D007668:Kidney; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020738:Leptin / Q000633:toxicity*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D020738:Leptin; D020011:Protective Agents; D012333:RNA, Messenger; D013481:Superoxides; D019255:NADPH Oxidases; D002331:Carnitine
keywords: L-CARNITINE; LEPTIN; NADPH OXIDASE; OXIDATIVE STRESS