HMGB1 is Secreted by 3T3-L1 Adipocytes Through JNK Signaling and the Secretion is Partially Inhibited by Adiponectin
HMGB1 is Secreted by 3T3-L1 Adipocytes Through JNK Signaling and the Secretion is Partially Inhibited by Adiponectin
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DOI：
10.1002/oby.21549
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发表时间：
2016-09-01
期刊：
影响因子：
6.9
通讯作者：
Maruyama, Ikuro
中科院分区：
文献类型：
--
作者：
Shimizu, Toshiaki;Yamakuchi, Munekazu;Maruyama, Ikuro
目的：肥胖是一种慢性炎症性疾病，脂肪细胞通过释放炎症介质参与肥胖相关炎症。高迁移率组框1 （HMGB1）是一种高度保守的dna结合蛋白，主要定位于细胞核，最近被认为是一种天然的促炎介质，当它被释放到细胞外时。假设HMGB1是一种脂肪细胞因子，在肥胖患者的白色脂肪组织（WAT）中作为先天促炎介质，并与胰岛素抵抗有关。此外，假设HMGB1的分泌受脂联素调节。方法：将3T3-L1细胞分化为成熟脂肪细胞。肿瘤坏死因子- α (tnf - α)刺激后，测定培养基中HMGB1的含量。采用免疫染色法检测HMGB1在3T3-L1脂肪细胞和人WAT中的定位。结果：tnf α诱导的3T3-L1脂肪细胞通过JNK信号通路分泌HMGB1。hmgb1激活MAP激酶（ERK1/2、JNK），抑制胰岛素刺激的3T3-L1脂肪细胞Akt磷酸化。1例肥胖患者3T3-L1脂肪细胞和WAT脂肪细胞的细胞质被HMGB1强烈染色。脂联素部分抑制tnf - α诱导的3T3-L1脂肪细胞分泌HMGB1。结论：HMGB1是一种促炎脂肪细胞因子，参与肥胖患者WAT炎症和胰岛素抵抗，可能促进代谢综合征的进展，脂联素可预防HMGB1诱导的脂肪组织炎症。
Objective: Obesity is a chronic inflammatory disease, and adipocytes contribute to obesity-associated inflammation by releasing inflammatory mediators. High mobility group box 1 (HMGB1), a highly conserved DNA-binding protein, mainly localized to cell nuclei, has been recently recognized as an innate pro-inflammatory mediator when released extracellularly. It was hypothesized that HMGB1 is an adipocytokine that acts as an innate pro-inflammatory mediator in white adipose tissue (WAT) of patients with obesity and is associated with insulin resistance. Additionally, it was hypothesized that HMGB1 secretion is regulated by adiponectin.Methods: 3T3-L1 cells were differentiated into mature adipocytes. After tumor necrosis factor-alpha (TNF-alpha) stimulation, HMGB1 in culture media was measured. Localizations of HMGB1 in 3T3-L1 adipocytes and human WAT were examined by immunostaining.Results: HMGB1 was secreted from TNF-alpha-induced 3T3-L1 adipocytes through JNK signaling. HMGB1-activated MAP kinases (ERK1/2, JNK) and suppressed insulin-stimulated Akt phosphorylation in 3T3-L1 adipocytes. The cytoplasm in 3T3-L1 adipocytes and adipocytes of WAT from a patient with obesity was intensely stained with HMGB1. Adiponectin partially inhibited TNF-alpha-induced HMGB1 secretion from 3T3-L1 adipocytes.Conclusions: These findings suggest that HMGB1 is a pro-inflammatory adipocytokine involved in WAT inflammation and insulin resistance in patients with obesity, which may contribute to the progression of metabolic syndrome, and that adiponectin protects against HMGB1-induced adipose tissue inflammation.