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.
Diabetes. 2011 Aug;60(8):2179-86. doi: 10.2337/db10-1210. Epub 2011 Jun 23.
The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance.
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.
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.
CD14 modulates adipose tissue inflammatory activity and insulin resistance.
本研究旨在评估巨噬细胞分子 CD14 与胰岛素抵抗之间的可能关系。
采用重组人可溶性 CD14（rh-sCD14），评估其对野生型（WT）小鼠、高脂喂养小鼠、ob/ob 小鼠和 CD14 敲除（KO）小鼠胰岛素敏感性（钳夹试验）和脂肪组织基因表达的影响。此外，还研究了 WT 小鼠接受 WT 供体来源的骨髓干细胞和 CD14 KO 小鼠骨髓干细胞移植后的情况。最后，评估了 CD14 在人脂肪组织中的表达情况以及人前脂肪细胞分化过程中的表达情况。
rh-sCD14 可增强 WT 小鼠、高脂喂养小鼠和 ob/ob 小鼠的胰岛素作用，但在 CD14 KO 小鼠中却无此作用，同时脂肪组织中有 3479 个基因的表达发生显著改变。与脂质代谢相关的基因家族的变化最为显著。接受 WT 供体来源骨髓干细胞移植的 WT 小鼠在高脂饮食后出现胰岛素抵抗，而接受 CD14 KO 小鼠骨髓干细胞移植的 WT 小鼠则抵抗了胰岛素抵抗的发生，同时肠系膜脂肪组织炎症基因表达降低。与接受 CD14 KO 供体来源骨髓干细胞移植的受体 KO 小鼠相比，接受高脂喂养 WT 小鼠来源骨髓干细胞移植的 CD14 KO 小鼠的葡萄糖耐量并未恶化。肥胖人群的全脂肪组织和脂肪细胞中 CD14 基因表达增加，肿瘤坏死因子-α进一步增加了其表达。
CD14 可调节脂肪组织炎症活性和胰岛素抵抗。
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