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Diabetes. 2015 Mar;64(3):856-66. doi: 10.2337/db14-0444. Epub 2014 Oct 3.

WISP1 is a novel adipokine linked to inflammation in obesity.

Author information

1
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.
2
Department of Medicine II, Section Molecular Hepatology-Alcohol Associated Diseases, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
3
Almazov Federal Medical Research Centre, Saint Petersburg, Russia.
4
Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
5
Department of Medicine, University of Leipzig, Leipzig, Germany.
6
Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin, Berlin, Germany.
7
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.
8
Medical Clinic III, Dresden University of Technology, Dresden, Germany.
9
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.
10
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.

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.

PMID:
25281430
DOI:
10.2337/db14-0444
[Indexed for MEDLINE]
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