Characterization of the Wnt Inhibitors Secreted Frizzled-Related Proteins (SFRPs) in Human Adipose Tissue

• DOI: 10.1210/jc.2012-3416
• Publication Date: 2013-02-08T07:12:54Z
• Authors: Anna Ehrlund; Niklas Mejhert; Silvia Lorente-Ce...; Gaby Åström; Ingrid Dahlman; Jurga Laurencikiene; Mikael Rydén
• Keywords: Male; 2. Zero hunger; 0301 basic medicine; Adolescent; Adipose Tissue, White; Adipocytes, White; Intracellular Signaling Peptides and Proteins; Gene Expression; Membrane Proteins; Cell Differentiation; Intra-Abdominal Fat; Frizzled Receptors; 03 medical and health sciences; Proto-Oncogene Proteins; Humans; Intercellular Signaling Peptides and Proteins; Obesity; Insulin Resistance; RNA, Small Interfering; Eye Proteins; Cells, Cultured; Adaptor Proteins, Signal Transducing; Glycoproteins

Wnt signaling regulates adipogenesis and adipocyte function. Secreted frizzled-related proteins (SFRPs) are a family of secreted (SFRP1-5) that bind inhibit Wnts. Several members, including SFRP5, have recently been implicated in dysfunction obesity.Our objective was to characterize the expression, secretion, function SFRP human white adipose tissue (WAT) fat cells.SFRP1-5 mRNA expression measured sc visceral WAT from lean obese individuals correlated insulin sensitivity. secretion explants assessed by ELISA. Gene SFRPs cultured adipocytes during after differentiation determined. Functional analyses were done gene silencing or incubations with recombinant SFRPs.SFRP1-4, but not levels altered obesity. However, although SFRP1 down-regulated positively sensitivity, SFRP2-4 up-regulated, particularly WAT, associated resistance. Only SFRP1, SFRP2, SFRP4 thereby constituting adipokines. Individual knockdowns did affect terminal differentiation. Incubations reduced proinflammatory cytokines IL-6 monocyte chemotactic protein-1 (MCP1) increased release adiponectin.SFRP1, adipokines, which correlates For this may be related effects on IL-6, MCP1, adiponectin. In contrast recent murine findings implicating SFRP5 metabolic dysfunction, is neither regulated obesity nor actively WAT.