Serum amyloid P and a DC-SIGN ligand inhibit high fat diet–induced adipose tissue and liver inflammation and steatosis in mice

Abstract High-fat diet (HFD)-induced inflammation is associated with a variety of health risks. The systemic pentraxin serum amyloid P (SAP) inhibits inflammation. SAP activates the high affinity IgG receptor Fcγ receptor I (FcγRI; CD64) and the lectin receptor DC-SIGN (CD209). Here, we show that for mice on a HFD, injections of SAP and a synthetic CD209 ligand (1866) reduced HFD-increased adipose and liver tissue inflammation, adipocyte differentiation, and lipid accumulation in adipose tissue. HFD worsened glucose tolerance tests and caused increased adipocyte size; for mice on a HFD, SAP improved glucose tolerance tests and reduced adipocyte size. Mice on a HFD had elevated serum levels of interleukin (IL)-1β, IL-23, interferon (IFN)-β, IFN-γ, MCP-1, and tumor necrosis factor-α. SAP reduced serum levels of IL-23, IFN-β, MCP-1, and tumor necrosis factor-α, whereas 1866 reduced IFN-γ. In vitro, SAP, but not 1866, treated cells isolated from white fat tissue (stromal vesicular fraction) produced the anti-inflammatory cytokine IL-10. HFD causes steatosis, and both SAP and 1866 reduced it. Conversely, compared to control mice, SAP knockout mice fed on a normal diet had increased white adipocyte cell sizes, increased numbers of inflammatory cells in adipose and liver tissue, and steatosis, and these effects were exacerbated on a HFD. SAP and 1866 may inhibit some but not all of the effects of a high fat diet.