title: Hepatic Macrosteatosis Is Partially Converted to Microsteatosis by Melatonin Supplementation in ob/ob Mice Non-Alcoholic Fatty Liver Disease.
abstract: BACKGROUND
  Obesity is a common risk factor for non-alcoholic fatty liver disease (NAFLD). Currently, there are no specific treatments against NAFLD. Thus, examining any molecule with potential benefits against this condition emerged melatonin as a molecule that influences metabolic dysfunctions. The aim of this study was to determine whether melatonin would function against NAFDL, studying morphological, ultrastuctural and metabolic markers that characterize the liver of ob/ob mice.
  
  
  METHODS
  Lean and ob/ob mice were supplemented with melatonin in the drinking water for 8 weeks. Histology and stereology were performed to assess hepatic steatosis and glycogen deposition. Ultrastructural features of mitochondria, endoplasmic reticulum (ER) and their juxtapositions were evaluated in livers of all experimental groups. Furthermore, hepatic distribution and expression of markers of ER and mitochondria (calnexin, ATP sintase β, GRP78 and CHOP) and metabolic dysfunction (RPB4, β-catenin) and cellular longevity (SIRT1) were analyzed.
  
  
  RESULTS
  Melatonin significantly reduced glycemia, identified also by a decrease of hepatic RBP4 expression, reversed macrosteatosis in microsteatosis at the hepatic pericentral zone, enlarged ER-mitochondrial distance and ameliorated the morphology and organization of these organelles in ob/ob mouse liver. Furthermore, in ob/ob mice, calnexin and ATP synthase β were partially restored, GRP78 and CHOP decreased in periportal and midzonal hepatocytes and β-catenin expression was, in part, restored in peripheral membranes of hepatocytes. Melatonin supplementation to ob/ob mice improves hepatic morphological, ultrastructural and metabolic damage that occurs as a result of NAFLD.
  
  
  CONCLUSIONS
  Melatonin may be a potential adjuvant treatment to limit NAFLD and its progression into irreversible complications.
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.|Interdipartimental University Center of Research "Adaption and Regeneration of Tissues and Organs- (ARTO)", University of Brescia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stacchiotti
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via A. Bianchi 7/9, 25124, Brescia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavazza
authors.affiliation: Center for Electron Microscopy, Faculty of Biology, University of Belgrade, Belgrade, Republic of Serbia.
authors.forename: Igor
authors.initials: I
authors.lastname: Golic
authors.affiliation: Center for Electron Microscopy, Faculty of Biology, University of Belgrade, Belgrade, Republic of Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Aleksic
authors.affiliation: Center for Electron Microscopy, Faculty of Biology, University of Belgrade, Belgrade, Republic of Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Korac
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.|Interdipartimental University Center of Research "Adaption and Regeneration of Tissues and Organs- (ARTO)", University of Brescia, Italy.
authors.forename: Luigi Fabrizio
authors.initials: LF
authors.lastname: Rodella
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.|Interdipartimental University Center of Research "Adaption and Regeneration of Tissues and Organs- (ARTO)", University of Brescia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D037281:Calnexin / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C495267:CTNNB1 protein, mouse; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D021122:Protein Subunits; D051176:beta Catenin; D037281:Calnexin; D051742:Transcription Factor CHOP; D012319:RNA Polymerase II; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C530489:ATP5b protein, mouse; D025261:Mitochondrial Proton-Translocating ATPases; D008550:Melatonin
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