title: CD14 modulates inflammation-driven insulin resistance.
abstract: OBJECTIVE
  The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance.
  
  
  METHODS
  The effects of recombinant human soluble CD14 (rh-sCD14) on insulin sensitivity (clamp procedure) and adipose tissue gene expression were evaluated in wild-type (WT) mice, high fat-fed mice, ob/ob mice, and CD14 knockout (KO) mice. We also studied WT mice grafted with bone marrow stem cells from WT donor mice and CD14 KO mice. Finally, CD14 was evaluated in human adipose tissue and during differentiation of human preadipocytes.
  
  
  RESULTS
  rh-sCD14 led to increased insulin action in WT mice, high-fat-fed mice, and ob/ob mice, but not in CD14 KO mice, in parallel to a marked change in the expression of 3,479 genes in adipose tissue. The changes in gene families related to lipid metabolism were most remarkable. WT mice grafted with bone marrow stem cells from WT donor mice became insulin resistant after a high-fat diet. Conversely, WT mice grafted with cells from CD14 KO mice resisted the occurrence of insulin resistance in parallel to decreased mesenteric adipose tissue inflammatory gene expression. Glucose intolerance did not worsen in CD14 KO mice grafted with bone marrow stem cells from high fat-fed WT mice when compared with recipient KO mice grafted with cells from CD14 KO donor mice. CD14 gene expression was increased in whole adipose tissue and adipocytes from obese humans and further increased after tumor necrosis factor-α.
  
  
  CONCLUSIONS
  CD14 modulates adipose tissue inflammatory activity and insulin resistance.
authors.affiliation: Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona, Biomedical Research Institute Dr Josep Trueta and CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain. jmfernandezreal.girona.ics@gencat.cat
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: Sofia
authors.initials: S
authors.lastname: Pérez del Pulgar
authors.forename: Elodie
authors.initials: E
authors.lastname: Luche
authors.forename: José Maria
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Aurelie
authors.initials: A
authors.lastname: Waget
authors.forename: Matteo
authors.initials: M
authors.lastname: Serino
authors.forename: Eleonora
authors.initials: E
authors.lastname: Sorianello
authors.forename: Alex
authors.initials: A
authors.lastname: Sánchez-Pla
authors.forename: Francesc Carmona
authors.initials: FC
authors.lastname: Pontaque
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Matilde R
authors.initials: MR
authors.lastname: Chacón
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: Remy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D004041:Dietary Fats / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha