CD14 Modulates Inflammation-Driven Insulin Resistance

  1. Antonio Zorzano3
  1. 1Section 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
  2. 2Unit of Endocrinology and Nutrition, University Hospital of Tarragona “Joan XXIII,” and CIBERDEM Tarragona, Tarragona, Spain
  3. 3Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Institute for Research in Biomedicine and CIBERDEM, Barcelona, Spain
  4. 4Institut National de la Santé et de la Recherche Médicale, Toulouse, France
  5. 5Université de Toulouse, UPS, Institut de Médecine Moléculaire de Rangueil, Toulouse, France
  6. 6Departament d’Estadística, Facultat de Biologia de la Universitat de Barcelona, Barcelona, Spain
  7. 7Unitat d’Estadística i Bioinformatica, Hospital Universitari Vall d’Hebrón, Barcelona, Spain
  1. Corresponding author: José Manuel Fernández-Real, jmfernandezreal.girona.ics{at}gencat.cat.

Abstract

OBJECTIVE The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance.

RESEARCH DESIGN AND 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.

Footnotes

  • Received August 26, 2010.
  • Accepted May 19, 2011.

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