Groupe d'Etude sur l'Inflammation Chronique et l'Obésité (GEICO), University of Reunion Island, CYROI, 2 rue Maxime Rivière, 97 490 Sainte-Clotilde, Reunion.
Cytokine. 2013 Oct;64(1):103-11. doi: 10.1016/j.cyto.2013.07.017. Epub 2013 Aug 9.
Low grade inflammation is one of the major metabolic disorders in case of obesity due to variable secretion of adipose derived cytokines called adipokines. Recently the nuclear protein HMGB1 was identified as an inflammatory alarmin in obesity associated diseases. However HMGB1 role in adipose tissue inflammation is not yet studied.
The aim of this study was to prove the expression of HMGB1 in human adipose tissue and to assess the levels of expression between normo-weight and obese individuals. Furthermore we determined which type of cells within adipose tissue is involved in HMGB1 production under inflammatory signal.
Western-blot was performed on protein lysates from human normo-weight and obese adipose tissue to study the differential HMGB1 expression. Human normo-weight adipose tissue, adipose-derived stromal cells (ASCs) and adipocytes were cultured and stimulated with LPS to induce inflammation. HMGB1, IL-6 and MCP-1 secretion and gene expression were quantified by ELISA and Q-PCR respectively, as well as cell death by LDH assay. HMGB1 translocation during inflammation was tracked down by immunofluorescence in ASCs.
HMGB1 was expressed 2-fold more in adipose tissue from obese compared to normo-weight individuals. LPS led to an up-regulation in HMGB1 secretion and gene expression in ASCs, while no change was noticed in adipocytes. Moreover, this HMGB1 release was not attributable to any cell death. In LPS-stimulated ASCs, HMGB1 translocation from nucleus to cytoplasm was detectable at 12h and the nuclear HMGB1 was completely drained out after 24h of treatment.
The expression level studies between adipose tissue from normo-weight and obese individuals together with in vitro results strongly suggest that adipose tissue secretes HMGB1 in response to inflammatory signals which characterized obesity.
由于脂肪细胞因子（称为脂肪因子）的分泌变化，低度炎症是肥胖症的主要代谢紊乱之一。最近，核蛋白 HMGB1 被鉴定为肥胖相关疾病中的炎症警报素。然而，HMGB1 在脂肪组织炎症中的作用尚未得到研究。
本研究旨在证明 HMGB1 在人体脂肪组织中的表达，并评估正常体重和肥胖个体之间的表达水平。此外，我们还确定了在炎症信号下，脂肪组织中哪种类型的细胞参与了 HMGB1 的产生。
对来自正常体重和肥胖人体脂肪组织的蛋白裂解物进行 Western blot，以研究 HMGB1 的差异表达。培养并刺激正常体重的人脂肪组织、脂肪衍生基质细胞（ASCs）和脂肪细胞，用 LPS 诱导炎症。通过 ELISA 和 Q-PCR 分别定量测定 HMGB1、IL-6 和 MCP-1 的分泌和基因表达，以及通过 LDH 测定法测定细胞死亡。通过 ASC 中的免疫荧光追踪炎症期间 HMGB1 的易位。
与正常体重个体相比，肥胖个体脂肪组织中 HMGB1 的表达增加了 2 倍。LPS 导致 ASCs 中 HMGB1 的分泌和基因表达上调，而在脂肪细胞中未观察到变化。此外，这种 HMGB1 释放与任何细胞死亡无关。在 LPS 刺激的 ASC 中，12 小时可检测到 HMGB1 从核易位到细胞质，并且在处理 24 小时后核 HMGB1 完全耗尽。
正常体重和肥胖个体脂肪组织之间的表达水平研究以及体外结果强烈表明，脂肪组织会对炎症信号作出反应而分泌 HMGB1，这是肥胖的特征。
