title: Melatonin reduces endoplasmic reticulum stress and autophagy in liver of leptin-deficient mice.
abstract: The sedentary lifestyle of modern society along with the high intake of energetic food has made obesity a current worldwide health problem. Despite great efforts to study the obesity and its related diseases, the mechanisms underlying the development of these diseases are not well understood. Therefore, identifying novel strategies to slow the progression of these diseases is urgently needed. Experimental observations indicate that melatonin has an important role in energy metabolism and cell signalling; thus, the use of this molecule may counteract the pathologies of obesity. In this study, wild-type and obese (ob/ob) mice received daily intraperitoneal injections of melatonin at a dose of 500 μg/kg body weight for 4 weeks, and the livers of these mice were used to evaluate the oxidative stress status, proteolytic (autophagy and proteasome) activity, unfolded protein response, inflammation and insulin signalling. Our results show, for the first time, that melatonin could significantly reduce endoplasmic reticulum stress in leptin-deficient obese animals and ameliorate several symptoms that characterize this disease. Our study supports the potential of melatonin as a therapeutic treatment for the most common type of obesity and its liver-associated disorders.
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Luxán-Delgado
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Yaiza
authors.initials: Y
authors.lastname: Potes
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Rubio-González
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Caballero
authors.affiliation: Geriatrics Service, Monte Naranco Hospital, Oviedo, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Solano
authors.affiliation: Geriatrics Service, Monte Naranco Hospital, Oviedo, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Fernández
authors.affiliation: Geriatrics Service, Monte Naranco Hospital, Oviedo, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bermúdez
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.|Neurology, Laboratory of Nutritional Investigation and Degenerative-Chronic Diseases (LINDCD), Federal University of Rio de Janeiro State - UNIRIO, Rio de Janeiro, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Rodrigues Moreira Guimarães
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.|CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
authors.forename: Ignacio
authors.identifier: http://orcid.org/0000-0003-1993-6725
authors.initials: I
authors.lastname: Vega-Naredo
authors.affiliation: Microbiology Department, Hospital Universitario Central de Asturias, Asturias, Oviedo, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Boga
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Coto-Montes
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D020738:Leptin / Q000172:deficiency*; D008099:Liver / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese
chemical_list: D020738:Leptin; D008550:Melatonin
keywords: autophagy; endoplasmic reticulum stress; leptin deficiency; melatonin; obesity