CD14 Modulates Inflammation-Driven Insulin Resistance

Abstract

OBJECTIVEThe study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance.RESEARCH DESIGN AND METHODSThe 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.RESULTSrh-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.CONCLUSIONSCD14 modulates adipose tissue inflammatory activity and insulin resistance.

Adipose Tissue and Serum CCDC80 in Obesity and Its Association with Related Metabolic Disease

“…To evaluate the inflammatory state of adipose tissue, we measured steadystate levels of CD14, a general macrophage marker (20) that is also an inflammation-related gene expressed in adipocytes (21). CD14 protein content relative to FAA was five-fold higher in VAT from obese than lean patients (P < 0.05), whereas no significant differences were observed in SAT depots ( Figure 1D).…”

A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction

“…Proinflammatory actions of lipopolysaccharide (LPS) are known to blunt insulin signalling and to prevent adipogenesis [7,8]. Several mediators of the LPS response (toll-like receptor 4 [TLR4] and cluster of differentiation 14 [CD14]) are increased in AT in association with metabolic disturbances and systemic inflammation [9,10].…”

Impacts métaboliques et inflammatoires des matières grasses émulsionnées

“…Dans le tissu adipeux également, une moindre expression des marqueurs inflammatoires et des récepteurs aux LPS était observée dans ce groupe. Or, il a été proposé que sCD14 puisse exercer des effets métaboliques bénéfiques dans le contexte de l'insulinorésistance induite par l'inflammation (Fernandez-Real et al, 2011). Ainsi, nos résultats suggèrent qu'un régime enrichi en huile de palme résulte en un transport plus actif et davantage pro-inflammatoire des LPS vers les tissus cibles via un taux élevé de LBP et une plus faible concentration plasmatique de sCD14.…”