Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance.
Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance.
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DOI：
10.4239/wjd.v8.i3.97
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发表时间：
2017-03-15
影响因子：
4.2
通讯作者：
Nikawa T
中科院分区：
文献类型：
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作者：
Abe T;Hirasaka K;Nikawa T
衰老和营养过剩导致啮齿动物和人类肥胖。众所周知，肥胖通过产生胰岛素抵抗（IR）而引起多种疾病。巨噬细胞浸润肥胖个体的脂肪组织（AT）并引起与IR相关的慢性低水平炎症。巨噬细胞浸润由AT中肥大脂肪细胞和免疫细胞释放的趋化因子调节。饱和脂肪酸被Toll样受体4（TLR 4）识别并诱导AT巨噬细胞（ATM）中的炎症反应。从活化的ATM释放的炎性细胞因子促进外周器官如肝脏、骨骼肌和AT中的IR。因此，ATM激活是肥胖IR的治疗靶点。泛素连接酶Casitas b-谱系淋巴瘤-b（Cbl-b）似乎有效地抑制巨噬细胞迁移和活化。Cbl-b在白细胞中高度表达，并负调节与迁移和活化相关的信号。Cbl-b缺乏增强了衰老和饮食诱导的肥胖小鼠的ATM积累和IR Cbl-b抑制ATM中的迁移相关信号和SFA诱导的TLR 4信号传导。因此，靶向Cbl-b可能是降低ATM激活诱导的IR的潜在治疗策略。本文就Cbl-b在ATM中的调控功能作一综述。
Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b (Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs.