title: Identification and validation of novel adipokines released from primary human adipocytes.
abstract: Adipose tissue is a major endocrine organ, releasing signaling and mediator proteins, termed adipokines, via which adipose tissue communicates with other organs. Expansion of adipose tissue in obesity alters adipokine secretion, which may contribute to the development of metabolic diseases. Although recent profiling studies have identified numerous adipokines, the amount of overlap from these studies indicates that the adipokinome is still incompletely characterized. Therefore, we conducted a complementary protein profiling on concentrated conditioned medium derived from primary human adipocytes. SDS-PAGE/liquid chromatography-electrospray ionization tandem MS and two-dimensional SDS-PAGE/matrix-assisted laser desorption ionization/time of flight MS identified 347 proteins, 263 of which were predicted to be secreted. Fourty-four proteins were identified as novel adipokines. Furthermore, we validated the regulation and release of selected adipokines in primary human adipocytes and in serum and adipose tissue biopsies from morbidly obese patients and normal-weight controls. Validation experiments conducted for complement factor H, αB-crystallin, cartilage intermediate-layer protein, and heme oxygenase-1 show that the release and expression of these factors in adipocytes is regulated by differentiation and stimuli, which affect insulin sensitivity, as well as by obesity. Heme oxygenase-1 especially reveals to be a novel adipokine of interest. In vivo, circulating levels and adipose tissue expression of heme oxygenase-1 are significantly increased in obese subjects compared with lean controls. Collectively, our profiling study of the human adipokinome expands the list of adipokines and further highlights the pivotal role of adipokines in the regulation of multiple biological processes within adipose tissue and their potential dysregulation in obesity.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Duesseldorf, Germany. Electronic address: stefan.lehr@ddz.uni-duesseldorf.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehr
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Duesseldorf, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartwig
authors.affiliation: Paul-Langerhans-Group, German Diabetes Center, Duesseldorf, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lamers
authors.affiliation: Paul-Langerhans-Group, German Diabetes Center, Duesseldorf, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Famulla
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
authors.forename: Franz-Georg
authors.initials: FG
authors.lastname: Hanisch
authors.affiliation: Department of Pathology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Cuvelier
authors.affiliation: Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ruige
authors.affiliation: Paul-Langerhans-Group, German Diabetes Center, Duesseldorf, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Eckardt
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Duesseldorf, Germany.
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.affiliation: Paul-Langerhans-Group, German Diabetes Center, Duesseldorf, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Sell
authors.affiliation: Paul-Langerhans-Group, German Diabetes Center, Duesseldorf, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Eckel
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000097:blood / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D009765:Obesity / Q000378:metabolism; D020543:Proteome; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D054392:Adipokines; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1