title: Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.
abstract: The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.
authors.affiliation: a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council , Naples , Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Caira
authors.affiliation: b Département de Chirurgie Digestive , Centre Hospitalier Universitarie de Nice , Nice , France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannelli
authors.affiliation: c Dipartimento di Scienze e Tecnologie , Università degli Studi del Sannio , Benevento , Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Sciarrillo
authors.affiliation: d Institute of Food Sciences, National Research Council , Avellino , Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Picariello
authors.affiliation: a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council , Naples , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Renzone
authors.affiliation: a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council , Naples , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.affiliation: e Service de Chirurgie Hépatique, Pancréatique, Biliaire et Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre , Université de Strasbourg, Hôpitaux Universitaires de Strasbourg , Strasbourg , France.
authors.forename: Pietro
authors.initials: P
authors.lastname: Addeo
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D055808:Drug Discovery; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D015415:Biomarkers; D011506:Proteins; D020543:Proteome
keywords: Obesity; human liver proteome; metabolic syndrome; oxidative stress; protein biomarkers