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[促红细胞生成素对高脂饮食小鼠棕色脂肪组织中PRDM16、FGF21表达及STAT磷酸化的影响]

[Effect of EPO on PRDM16, FGF21 expression and STAT phosphorylation of brown adipose tissue in HFD mice].

作者信息

Zhang Rui, Chen Lu, Ge Jun-Mei, Ma Gen-Shan, Cai Jun-Yan

机构信息

Zhongda Hospital, Southeast University, Nanjing 210009, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Apr 8;34(4):294-298. doi: 10.12047/j.cjap.5654.2018.068.

Abstract

OBJECTIVE

To investigate the effect of erythropoietin (EPO) on blood glucoseand plasma insulin level, index of insulin resistance (HOMA-IR), introperitoneal glucose tolerance test (IPGTT), the mRNA and protein level of PR domain-containing 16 (PRDM16), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), fibroblast growth factor 21 (FGF21) of brown adipose tissue (BAT) in mice fed with high fat diet (HFD) in order to provide clues for the mechanism of obesity and complication.

METHODS

Twenty C57BL/6J male mice fed with HFD were randomly divided into control group (HFD-Con) and EPO group (HFD-EPO), mice in the two groups were injected intraperitoneally normal saline and EPO (200 IU/kg) res pectively, 3 times per week for consecutive 4 weeks.Then the body weight, blood glucose, plasma insulin level, HOMA-IR and IPGTT were detected.The mRNA and protein level of PRDM16, FGF21, p-STAT3/STAT3 in brown adipose tissue were detected by real-time quantitative RT-PCR and Western blot respectively.

RESULTS

After intraperitoneal injection of EPO for 4 weeks, the body weight of the mice in HFD-EPO and HFD-Con groups was (26.65±0.85) g and (31.50±1.6 0) g respectively.The blood glucose of the mice in HFD-EPO group[(62.79±8.09) mg/dl]was significantly decreased compared with that in HFD-Con group[(91.06±9.86) mg/dl].The plasmainsulin level in HFD-EPO group[(10.56±1.06)μU/ml]was significantly decreased compared with that in HFD-Con group[(13.2±1.1)μU/ml, < 0.01].The level of IPGTT in HFD-EPO group was significantly ameliorated and th e HOMA-IR decreased compared with those in HFD-Con group.The mRNA and protein expressions of PRDM16, FGF21 and the level of STAT3 of brown adipose tissue in HFD-E PO group were increased obviously.And there was no difference of FGF21 mRNA content in liver and FGF21 content in plasmabetween the two groups.

CONCLUSIONS

EPO could promote differentiation of brown adipose tissue by increase in the express ion of PRDM16, and decrease the blood glucose level, ameliorate glucose metabolism in obses mice.

摘要

目的

探讨促红细胞生成素(EPO)对高脂饮食(HFD)喂养小鼠血糖、血浆胰岛素水平、胰岛素抵抗指数(HOMA-IR)、腹腔葡萄糖耐量试验(IPGTT)、棕色脂肪组织(BAT)中含PR结构域16(PRDM16)、磷酸化信号转导子和转录激活子3(p-STAT3)、成纤维细胞生长因子21(FGF21)的mRNA和蛋白水平的影响,为肥胖及其并发症的机制提供线索。

方法

将20只高脂饮食喂养的C57BL/6J雄性小鼠随机分为对照组(HFD-Con)和EPO组(HFD-EPO),两组小鼠分别腹腔注射生理盐水和EPO(200 IU/kg),每周3次,连续4周。然后检测体重、血糖、血浆胰岛素水平、HOMA-IR和IPGTT。分别采用实时定量RT-PCR和Western blot检测棕色脂肪组织中PRDM16、FGF21、p-STAT3/STAT3的mRNA和蛋白水平。

结果

腹腔注射EPO 4周后,HFD-EPO组和HFD-Con组小鼠体重分别为(26.65±0.85)g和(31.50±1.60)g。HFD-EPO组小鼠血糖[(62.79±8.09)mg/dl]较HFD-Con组[(91.06±9.86)mg/dl]显著降低。HFD-EPO组血浆胰岛素水平[(10.56±1.06)μU/ml]较HFD-Con组[(13.2±1.1)μU/ml,P<0.01]显著降低。与HFD-Con组相比,HFD-EPO组IPGTT水平显著改善,HOMA-IR降低。HFD-EPO组棕色脂肪组织中PRDM16、FGF21的mRNA和蛋白表达以及STAT3水平明显升高。两组肝脏FGF21 mRNA含量和血浆FGF21含量无差异。

结论

EPO可通过增加PRDM16的表达促进棕色脂肪组织分化,降低肥胖小鼠血糖水平,改善糖代谢。

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