Xing Baoheng, Wang Lili, Li Qin, Cao Yalei, Dong Xiujuan, Liang Jun, Wu Xiaohua
Department of Obstetrics, Cangzhou City Central Hospital, Cangzhou, 061001, China.
Department of Neurology, Cangzhou City People's Hospital, Cangzhou, 061000, China.
J Physiol Biochem. 2015 Dec;71(4):649-58. doi: 10.1007/s13105-015-0430-z. Epub 2015 Aug 29.
Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the last decade, affecting about 2 to 5% pregnant women. Even among women who have gestational hyperglycemia may also be positively related to adverse outcomes as GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with diabetes and insulin resistance and its expression was reported to be negatively regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a role in a gestational hyperglycemia mouse model. Mice were divided into non-pregnant and pregnant groups, and each comprised three subgroups: control, high-fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of triglycerides, total cholesterol, glucose, and insulin, as well as conducted thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides, total cholesterol, glucose, and insulin levels in the serum. Additionally, thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship correlation between Hsp70 and BAT functions. Hsp70 level is associated with hyperglycemia during pregnancy. Our results support the role of Hsp70 in facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3 pathway.
妊娠糖尿病（GDM）在过去十年中已成为一种流行病，影响约2%至5%的孕妇。即使在患有妊娠高血糖的女性中，其不良后果也可能与GDM呈正相关。由于热休克蛋白（Hsp）70已被报道与糖尿病和胰岛素抵抗有关，并且据报道其表达受膜通透性Hsp70抑制剂MAL3 - 101负调控，而受Hsp70激活剂BGP - 15正调控，我们研究了Hsp70在妊娠高血糖小鼠模型中是否发挥作用。将小鼠分为非妊娠组和妊娠组，每组又包含三个亚组：对照组、高脂饮食（HFD） + MAL3 - 101组和HFD + BGP - 15组。我们检测了血清甘油三酯、总胆固醇、葡萄糖和胰岛素水平，并对棕色脂肪组织（BAT）进行了热检测。还通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）分析和半胱天冬酶 - 3染色研究了Hsp70在BAT细胞凋亡中的作用。在喂食HFD的小鼠中，较高的血清Hsp70水平与妊娠后体重增加有关。与对照非妊娠小鼠相比，对照妊娠小鼠的循环Hsp70升高。BGP诱导的血清Hsp70表达降低了血清中的甘油三酯、总胆固醇、葡萄糖和胰岛素水平。此外，BAT的热检测、TUNEL和半胱天冬酶 - 3染色揭示了Hsp70与BAT功能之间的关系相关性。Hsp70水平与妊娠期间的高血糖有关。我们的结果支持Hsp70在促进BAT活动和通过半胱天冬酶 - 3途径保护BAT细胞免于凋亡方面的作用。
