title: WISP1 is a novel adipokine linked to inflammation in obesity.
abstract: WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Veronica
authors.initials: V
authors.lastname: Murahovschi
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Pivovarova
authors.affiliation: Department of Medicine II, Section Molecular Hepatology-Alcohol Associated Diseases, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Iryna
authors.initials: I
authors.lastname: Ilkavets
authors.affiliation: Almazov Federal Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Dmitrieva
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Döcke
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Keyhani-Nejad
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Gögebakan
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Osterhoff
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Margrit
authors.initials: M
authors.lastname: Kemper
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hornemann
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Mariya
authors.initials: M
authors.lastname: Markova
authors.affiliation: Department of Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stockmann
authors.affiliation: Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, and Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, U.K.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.affiliation: Medical Clinic III, Dresden University of Technology, Dresden, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lamounier-Zepter
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.affiliation: Almazov Federal Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Konradi
authors.affiliation: Department of Medicine II, Section Molecular Hepatology-Alcohol Associated Diseases, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Integrated Research and Treatment Center, Center for Sepsis Control and Care, Friedrich Schiller University, and Department of Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: von Loeffelholz
authors.affiliation: Department of Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany rudovich@dife.de.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rudovich
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D059630:Mesenchymal Stem Cells; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D054392:Adipokines; D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; C492067:CCN4 protein, mouse; D011518:Proto-Oncogene Proteins