Heat shock protein 60 as a mediator of adipose tissue inflammation and insulin resistance.
Heat shock protein 60 as a mediator of adipose tissue inflammation and insulin resistance.
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作者：
Märker T;Sell H;Zillessen P;Glöde A;Kriebel J;Ouwens DM;Pattyn P;Ruige J;Famulla S;Roden M;Eckel J;Habich C
应激蛋白热休克蛋白60（Hsp 60）诱导小鼠脂肪细胞分泌促炎介质。本研究旨在研究热休克蛋白60作为脂肪组织炎症和骨骼肌细胞（SkMC）胰岛素敏感性的介质，并定量血浆中的热休克蛋白60浓度在瘦和肥胖个体。在人脂肪细胞和SkMCs中测量Hsp 60释放和Hsp 60诱导的细胞因子分泌和信号传导的调节。脂肪细胞比前脂肪细胞和SkMCs表现出更高的Hsp 60释放，这进一步被细胞因子和Toll样受体（TLR）-4激活所刺激。Hsp 60激活细胞外信号相关激酶（ERK）-1/2、Jun NH 2-末端激酶（JNK）、p38、核因子（NF）-κB，并损害脂肪细胞中胰岛素刺激的Akt磷酸化。此外，Hsp 60刺激脂肪细胞分泌肿瘤坏死因子-α、白细胞介素（IL）-6和IL-8。在SkMCs中，Hsp 60激活ERK 1/2、JNK和NF-κB，并抑制胰岛素信号传导和胰岛素刺激的葡萄糖摄取。SkMCs在Hsp 60刺激下释放IL-6、IL-8和单核细胞趋化蛋白-1。血浆Hsp 60在肥胖男性中高于瘦男性，并与BMI、血压、瘦素和稳态模型评估胰岛素抵抗呈正相关。总之，Hsp 60由人脂肪细胞释放，在肥胖人的血浆中增加，并诱导胰岛素抵抗。这伴随着人脂肪细胞和SkMC中促炎信号传导的激活。因此，热休克蛋白60可能是一个潜在的脂肪组织炎症和肥胖相关的代谢紊乱的因素。
The stress protein heat shock protein 60 (Hsp60) induces secretion of proinflammatory mediators from murine adipocytes. This study aimed to study Hsp60 as a mediator of adipose tissue inflammation and skeletal muscle cell (SkMC) insulin sensitivity and to quantify plasma Hsp60 concentrations in lean and obese individuals. Regulation of Hsp60 release and Hsp60-induced cytokine secretion and signaling was measured in human adipocytes and SkMCs. Adipocytes exhibited higher Hsp60 release than preadipocytes and SkMCs, which was further stimulated by cytokines and Toll-like receptor (TLR)-4 activation. Hsp60 activated extracellular signal–related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK), p38, nuclear factor (NF)-κB, and impaired insulin-stimulated Akt phosphorylation in adipocytes. Furthermore, Hsp60 stimulated adipocytes to secrete tumor necrosis factor-α, interleukin (IL)-6, and IL-8. In SkMCs, Hsp60 activated ERK1/2, JNK, and NF-κB and inhibits insulin signaling and insulin-stimulated glucose uptake. SkMCs released IL-6, IL-8, and monocyte chemoattractant protein-1 on Hsp60 stimulation. Plasma Hsp60 was higher in obese males than in lean males and correlated positively with BMI, blood pressure, leptin, and homeostasis model assessment–insulin resistance. In summary, Hsp60 is released by human adipocytes, increased in plasma of obese humans, and induces insulin resistance. This is accompanied by activation of proinflammatory signaling in human adipocytes and SkMCs. Thus, Hsp60 might be a factor underlying adipose tissue inflammation and obesity-associated metabolic disorders.
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