Exp Clin Endocrinol Diabetes 2014; 122 - P049
DOI: 10.1055/s-0034-1372066

Wnt1 inducible signaling pathway protein 1 (WISP1) is a novel adipokine linked to inflammation and insulin resistance in visceral fat

V Murahovschi 1, 2, O Pivovarova 1, 2, I Ilkavets 3, S Döcke 1, 2, R Dmitrieva 4, F Keyhani Nejad 1, 2, Ö Gögebakan 1, 2, M Osterhoff 1, 2, N Klöting 5, M Stockmann 6, P Neuhaus 6, A Conradi 4, S Dooley 3, C von Loeffelholz 6, 7, M Blüher 5, AFH Pfeiffer 1, 2, N Rudovich 1, 2
  • 1Deutsches Institut für Ernährungsforschung (DIfE) Potsdam-Rehbrücke, Department of Clinical Nutrition, Nuthetal, Germany
  • 2Charité Universitätsmedizin, Department of Endocrinology Diabetes and Nutrition, Campus Benjamin Franklin, Berlin, Germany
  • 3Medical Clinic II, Universitätsmedizin Mannheim, University of Heidelberg, Department of Molecular Hepatology and Alcohol-dependent Liver Diseases, Mannheim, Germany
  • 4Almazov Federal Center of Heart, Blood and Endocrinology, Saint Petersburg, Russian Federation
  • 5University of Leipzig, Department of Medicine, Leipzig, Germany
  • 6Charité – Universitätsmedizin, Department of General, Visceral and Transplantation Surgery, Berlin, Germany
  • 7Jena University Hospital, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena, Germany

Introduction: WISP1 is a member of the CCN family of extracellular matrix proteins and target gene of Wnt signaling pathway. Here we show that WISP1 is released from adipocytes and WISP1 expression correlate with weight loss and signs of insulin resistance.

Methods: The mRNA expression of WISP1 was studied 1) in paired samples of visceral (VAT) and subcutaneous (SAT) adipose tissue from healthy subjects (n = 75); 2) in paired VAT, SAT and liver tissue from subjects with/without NAFLD (n = 47); 3) in overweight subjects underwent weight reduction (DiOGenes study, n = 49); 4) in human stem cell derived adipocytes, in human monocytes and in M-and GM-macrophages. WISP1 protein levels were measured in plasma and in cell culture medium of differentiated adipocytes. Gene expression of inflammation marker TNFα, NFkB, IL-6 was mesured in differentiated adipocytes after stimulation with 1 µg/ml WISP1 for 4h.

Results: WISP1 protein was identified in cell culture medium of differentiated adipocytes. Expression of WISP1 was not detectable in monocytes and in M-and GM-macrophages. A significant increase of IL-6, NFkB and TNFα expression in differentiated adipocytes after 4h stimulation with 1 µg/ml WISP1 was observed. In human studies: 1) we found a correlation between insulin sensitivity, macrophages infiltration, adiponectin levels and WISP1 expression in VAT and SAT samples; 2) WISP1 expression is higher in VAT than in SAT; 3) hepatic WISP1 expression has no association with ectopic fat accumulation in obesity; 4) weight loss decreases WISP1 expression in SAT and circulating WISP1 levels in plasma.

Discussion: Our data show that WISP1 is a novel adipokine but not hepatokine that is overexpressed in visceral fat from obese subjects and reflects insulin resistance and adipose tissue inflammation. Weight changes regulate circulating WISP1 levels and WISP1 expression in adipose tissue. Therefore, we propose that WISP1 is a novel biomarker that links between obesity and metabolic syndrome.