Characterization of the Wnt inhibitors secreted frizzled-related proteins (SFRPs) in human adipose tissue.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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. Our objective was to characterize the expression, secretion, and function of the SFRP family in human white adipose tissue (WAT) and fat cells. 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. 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

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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