Diabetes Research Centre, Qatar Biomedical Research Institute, Box: 5825, Doha, Qatar.
Lipids Health Dis. 2014 Jul 1;13:106. doi: 10.1186/1476-511X-13-106.
Obesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels.
Two groups of adult non-diabetic human subjects consisting of lean and obese (n = 47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP-40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRT-PCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects.
Obese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P < 0.05). No differential expression was observed for HSP-27 between the two groups. Higher levels of HSP-72 and GRP-94 proteins correlated positively with the indices of obesity (body mass index and percent body fat) and circulating levels of IFN-gamma-inducible protein 10 (IP-10) and RANTES chemokines. This expression pattern was concomitant with increased inflammatory response in the adipose tissue as monitored by increased levels of Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and RANTES (P < 0.05). Physical exercise reduced the expression of various HSPs in obese to normal levels observed in lean subjects with a parallel decrease in the endogenous levels of IL-6, TNF-α, and RANTES.
Taken together, these data indicate that obesity triggers differential regulation of various components of the HSR in non-diabetic subjects and a 3-month physical moderate exercise was sufficient to restore the normal expression of HSPs in the adipose tissue with concomitant attenuation in the inflammatory response.
肥胖的特征是慢性低度炎症和关键代谢组织中应激反应的改变。热休克反应（HSR）的损害已经与糖尿病和胰岛素抵抗有关，表现为热休克蛋白（HSPs）表达减少。然而，非糖尿病肥胖人群的 HSR 状况尚未阐明。本研究旨在探讨肥胖是否会引发 HSR 模式的变化，以及运动对这种模式在蛋白质和 mRNA 水平上的影响。
本研究纳入了两组成年非糖尿病肥胖者（每组 47 人）和非肥胖者。通过免疫组织化学首先研究脂肪组织中 HSP-27、DNAJB3/HSP-40、HSP-60、HSC-70、HSP72、HSP-90 和 GRP-94 的表达模式，然后通过 Western blot 和 qRT-PCR 补充外周血单核细胞（PBMCs）中的 HSPs 表达模式。还分析了 HSPs 表达水平与各种生理、临床和生化参数的相关性。我们还探讨了 3 个月适度运动对肥胖者 HSPs 表达模式的影响。
肥胖者 HSP-60、HSC-70、HSP-72、HSP-90 和 GRP-94 的表达增加，DNAJB3/HSP-40 的表达降低（P<0.05）。两组之间 HSP-27 的表达无差异。HSP-72 和 GRP-94 蛋白水平较高与肥胖指数（体重指数和体脂百分比）和循环干扰素γ诱导蛋白 10（IP-10）和 RANTES 趋化因子水平呈正相关。这种表达模式与脂肪组织中炎症反应的增加有关，表现为白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和 RANTES 水平升高（P<0.05）。运动使肥胖者 HSPs 的表达降低至瘦者水平，同时使内源性 IL-6、TNF-α 和 RANTES 水平降低。
综上所述，这些数据表明，肥胖会引发非糖尿病患者 HSR 各成分的差异调节，3 个月的适度运动足以恢复脂肪组织中 HSPs 的正常表达，并伴随炎症反应的减弱。
