Lagathu C, Yvan-Charvet L, Bastard J-P, Maachi M, Quignard-Boulangé A, Capeau J, Caron M
INSERM, U680, Université Pierre et Marie Curie (UPMC-Paris 6), Faculty of Medicine, 27 rue Chaligny, 75012, Paris, France.
Diabetologia. 2006 Sep;49(9):2162-73. doi: 10.1007/s00125-006-0335-z. Epub 2006 Jul 25.
AIMS/HYPOTHESIS: Adipose tissue inflammation has recently been implicated in the pathogenesis of insulin resistance and is probably linked to high local levels of cytokines. IL1B, a proinflammatory cytokine, may participate in this alteration.
We evaluated the chronic effect (1-10 days) of IL1B (0.1-20 ng/ml) on insulin signalling in differentiating 3T3-F442A and differentiated 3T3-L1 murine adipocytes and in human adipocytes. We also assessed expression of the gene encoding IL1B in adipose tissue of wild-type and insulin-resistant mice (diet-induced and genetically obese ob/ob mice).
IL1B inhibited insulin-induced phosphorylation of the insulin receptor beta subunit, insulin receptor substrate 1, Akt/protein kinase B and extracellular regulated kinase 1/2 in murine and human adipocytes. Accordingly, IL1B suppressed insulin-induced glucose transport and lipogenesis. Long-term treatment of adipose cells with IL1B decreased cellular lipid content. This could result from enhanced lipolysis and/or decreased expression of genes involved in lipid metabolism (acetyl-CoA carboxylase, fatty acid synthase). Down-regulation of peroxisome proliferating-activated receptor gamma and CCAAT/enhancer-binding protein alpha in response to IL1B may have contributed to the altered phenotype of IL1B-treated adipocytes. Moreover, IL1B altered adipocyte differentiation status in long-term cultures. IL1B also decreased the production of adiponectin, an adipocyte-specific protein that plays a positive role in insulin sensitivity. Expression of the gene encoding IL1B was increased in epididymal adipose tissue of obese insulin-resistant mice.
CONCLUSIONS/INTERPRETATION: IL1B is upregulated in adipose tissue of obese and insulin-resistant mouse models and may play an important role in the development of insulin resistance in murine and human adipose cells.
目的/假设：脂肪组织炎症最近被认为与胰岛素抵抗的发病机制有关，可能与局部细胞因子水平升高有关。白细胞介素1β（IL1B）作为一种促炎细胞因子，可能参与了这种改变。
我们评估了IL1B（0.1 - 20 ng/ml）对分化中的3T3 - F442A和分化后的3T3 - L1小鼠脂肪细胞以及人脂肪细胞中胰岛素信号传导的慢性影响（1 - 10天）。我们还评估了野生型和胰岛素抵抗小鼠（饮食诱导和基因肥胖ob/ob小鼠）脂肪组织中编码IL1B的基因表达。
IL1B抑制了小鼠和人脂肪细胞中胰岛素诱导的胰岛素受体β亚基、胰岛素受体底物1、Akt/蛋白激酶B和细胞外调节激酶1/2的磷酸化。相应地，IL1B抑制了胰岛素诱导的葡萄糖转运和脂肪生成。用IL1B长期处理脂肪细胞会降低细胞脂质含量。这可能是由于脂肪分解增强和/或参与脂质代谢的基因（乙酰辅酶A羧化酶、脂肪酸合酶）表达降低所致。过氧化物酶体增殖物激活受体γ和CCAAT/增强子结合蛋白α对IL1B的下调反应可能导致了经IL1B处理的脂肪细胞表型改变。此外，IL1B在长期培养中改变了脂肪细胞的分化状态。IL1B还降低了脂联素的产生，脂联素是一种在胰岛素敏感性中起积极作用的脂肪细胞特异性蛋白。肥胖胰岛素抵抗小鼠附睾脂肪组织中编码IL1B的基因表达增加。
结论/解读：在肥胖和胰岛素抵抗小鼠模型的脂肪组织中，IL1B表达上调，可能在小鼠和人脂肪细胞胰岛素抵抗的发展中起重要作用。
