在缺乏髓样分化因子88（MyD88）的情况下，C型凝集素受体-1（Dectin-1）激活会加剧肥胖和胰岛素抵抗。
Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88.
作者信息
Castoldi Angela, Andrade-Oliveira Vinicius, Aguiar Cristhiane Favero, Amano Mariane Tami, Lee Jennifer, Miyagi Marcelli Terumi, Latância Marcela Teatin, Braga Tarcio Teodoro, da Silva Marina Burgos, Ignácio Aline, Carola Correia Lima Joanna Darck, Loures Flavio V, Albuquerque José Antonio T, Macêdo Marina Barguil, Almeida Rafael Ribeiro, Gaiarsa Jonas W, Luévano-Martínez Luis A, Belchior Thiago, Hiyane Meire Ioshie, Brown Gordon D, Mori Marcelo A, Hoffmann Christian, Seelaender Marília, Festuccia Willian T, Moraes-Vieira Pedro Manoel, Câmara Niels Olsen Saraiva
机构信息
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
出版信息
Cell Rep. 2017 Jun 13;19(11):2272-2288. doi: 10.1016/j.celrep.2017.05.059.
The underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans.
髓样分化因子88（MyD88）调节肥胖、代谢性炎症和胰岛素抵抗（IR）发生发展的潜在机制尚不清楚。在高脂饮食（HFD）喂养的小鼠中，全局敲除MyD88会导致体重增加、葡萄糖稳态受损、脂肪组织（AT）中Dectin-1表达升高以及促炎性CD11c+ AT巨噬细胞（ATM）增多。Dectin-1基因敲除小鼠可免受饮食诱导的肥胖（DIO）和IR影响，且CD11c+ AT巨噬细胞减少。Dectin-1拮抗剂可改善正常饮食和HFD喂养的MyD88基因敲除小鼠的葡萄糖稳态，并减少CD11c+ AT巨噬细胞。Dectin-1激动剂会使MyD88基因敲除小鼠的葡萄糖稳态恶化。肥胖个体AT中Dectin-1表达增加。总之，我们的数据表明，在缺乏MyD88的情况下，Dectin-1通过促进CD11c+ AT巨噬细胞来调节AT炎症，并确定了Dectin-1在肥胖等慢性炎症状态中的作用。这表明Dectin-1作为人类代谢失调的生物标志物可能具有治疗意义。
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