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Publication : Serum Amyloid P and a Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin Ligand Inhibit High-Fat Diet-Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice.

First Author  Pilling D Year  2019
Journal  Am J Pathol Volume  189
Issue  12 Pages  2400-2413
PubMed ID  31539521 Mgi Jnum  J:286673
Mgi Id  MGI:6388219 Doi  10.1016/j.ajpath.2019.08.005
Citation  Pilling D, et al. (2019) Serum Amyloid P and a Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin Ligand Inhibit High-Fat Diet-Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice. Am J Pathol 189(12):2400-2413
abstractText  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 Fcgamma receptor I (FcgammaRI; CD64) and the lectin receptor dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN; CD209). Herein, we show that for mice on an 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 test results and caused increased adipocyte size; for mice on an HFD, SAP improved glucose tolerance test results and reduced adipocyte size. Mice on an HFD had elevated serum levels of IL-1beta, IL-23, interferon (IFN)-beta, IFN-gamma, monocyte chemoattractant protein 1 [MCP-1; chemokine (C-C motif) ligand 2 (CCL2)], and tumor necrosis factor-alpha. SAP reduced serum levels of IL-23, IFN-beta, MCP-1, and tumor necrosis factor-alpha, whereas 1866 reduced IFN-gamma. 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 with 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 an HFD. SAP and 1866 may inhibit some, but not all, of the effects of a high-fat diet.
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