title: Characterization of the Wnt inhibitors secreted frizzled-related proteins (SFRPs) in human adipose tissue.
abstract: BACKGROUND
  Wnt signaling regulates adipogenesis and adipocyte function. Secreted frizzled-related proteins (SFRPs) are a family of secreted proteins (SFRP1-5) that bind and inhibit Wnts. Several members, including SFRP5, have recently been implicated in adipocyte dysfunction in obesity.
  
  
  OBJECTIVE
  Our objective was to characterize the expression, secretion, and function of the SFRP family in human white adipose tissue (WAT) and fat cells.
  
  
  METHODS
  SFRP1-5 mRNA expression was measured in human sc and visceral WAT from lean and obese individuals and correlated to insulin sensitivity. SFRP secretion from WAT explants was assessed by ELISA. Gene expression of SFRPs in cultured adipocytes during and after differentiation was determined. Functional analyses were done by gene silencing or incubations with recombinant SFRPs.
  
  
  RESULTS
  SFRP1-4, but not SFRP5, mRNA levels were altered in obesity. However, although SFRP1 was down-regulated and correlated positively with insulin sensitivity, SFRP2-4 were up-regulated, particularly in visceral WAT, and associated with insulin resistance. Only SFRP1, SFRP2, and SFRP4 were secreted from WAT, thereby constituting adipokines. Individual knockdowns of SFRP1, SFRP2, or SFRP4 during adipogenesis did not affect terminal differentiation. Incubations with SFRP1 reduced the secretion of the proinflammatory cytokines IL-6 and monocyte chemotactic protein-1 (MCP1) and increased the release of adiponectin.
  
  
  CONCLUSIONS
  SFRP1, SFRP2, and SFRP4 are adipokines, the expression of which correlates with insulin sensitivity. For SFRP1, this may be related to effects on the secretion of IL-6, MCP1, and adiponectin. In contrast to recent murine findings implicating SFRP5 in metabolic dysfunction, this SFRP is neither regulated by obesity nor actively secreted from human WAT.
authors: Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden. anna.ehrlund@ki.se
authors: Anna
authors: A
authors: Ehrlund
authors: Niklas
authors: N
authors: Mejhert
authors: Silvia
authors: S
authors: Lorente-Cebrián
authors: Gaby
authors: G
authors: Aström
authors: Ingrid
authors: I
authors: Dahlman
authors: Jurga
authors: J
authors: Laurencikiene
authors: Mikael
authors: M
authors: Rydén
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology; D000293:Adolescent; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D050151:Subcutaneous Fat / Q000166:cytology; D060449:Wnt Signaling Pathway / Q000502:physiology*; D000099274:Frizzled-Related Proteins; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D051157:Frizzled Receptors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000099274:Frizzled-Related Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C109618:SFRP2 protein, human; C118723:SFRP4 protein, human; C118511:SFRP5 protein, human