EPO对高脂喂养小鼠棕色脂肪组织PRDM16、FGF21表达及STAT3磷酸化水平的影响

doi:10.12047/j.cjap.5654.2018.068

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (4): 294-298.doi: 10.12047/j.cjap.5654.2018.068

EPO对高脂喂养小鼠棕色脂肪组织PRDM16、FGF21表达及STAT3磷酸化水平的影响

张睿, 陈璐, 葛俊美, 马根山, 蔡君艳

东南大学附属中大医院, 江苏南京 210009

收稿日期:2017-10-20 修回日期:2018-01-21 出版日期:2018-07-28 发布日期:2019-02-21
通讯作者: 蔡君艳 E-mail:tuziguai2007@126.com
基金资助:
国家自然科学基金资助项目（81600677）

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

ZHANG Rui, CHEN Lu, GE Jun-mei, MA Gen-shan, CAI Jun-yan

Zhongda Hospital, Southeast University, Nanjing 210009, China

Received:2017-10-20 Revised:2018-01-21 Online:2018-07-28 Published:2019-02-21
Supported by:
国家自然科学基金资助项目（81600677）

摘要/Abstract

摘要： 目的：探索促红细胞生成素（EPO）对高脂饲料（HFD）喂养小鼠血糖和血浆胰岛素水平、胰岛素抵抗指数（HOMA-IR）、糖耐量，以及棕色脂肪组织中含PR结构域蛋白16（PRDM16）、信号转导与转录激活因子3（STAT3）磷酸化水平（p-STAT3/STAT3）、成纤维细胞生长因子21（FGF21）mRNA以及蛋白质表达的影响，为肥胖及其并发症的发生机制提供线索。方法：20只高脂饲料喂养的C57BL/6J雄性小鼠随机分为对照组（HFD-Con）和EPO组（HFD-EPO），两组分别腹腔注射生理盐水和EPO（200 IU/kg），每周3次，连续4周。4周后检测两组动物的体重、血糖与血浆胰岛素水平、HOMA-IR及糖耐量的变化；分别使用实时定量PCR法和Western blot法检测棕色脂肪组织中PRDM16、STAT3、FGF21 mRNA和蛋白质水平。结果：腹腔注射EPO 4周后，HFD-EPO组小鼠体重为（26.65±0.85）g，HFD-Con组体重为（31.50±1.60）g，P<0.01。HFD-Con组血糖为（91.06±9.86）mg/dl，HFD-EPO组为（62.79±8.09）mg/dl，P<0.01；HFD-EPO组小鼠血浆胰岛素水平为（10.56±1.06）μU/ml，HFD-Con组为（13.2±1.1）μU/ml，P<0.01。与HFD-Con组比较，HFD-EPO组的糖耐量水平显著改善，胰岛素抵抗指数下降；HFD-EPO组动物棕色脂肪组织中PRDM16、FGF21mRNA以及蛋白质表达，p-STAT/STAT3水平均显著增加，两组小鼠肝脏中FGF21 mRNA含量、血浆中FGF21含量无明显差异。结论：EPO可能通过增加棕色脂肪组织中PRDM16表达促进棕色脂肪组织的分化，降低高脂喂养小鼠的血糖水平、改善高脂喂养小鼠的糖代谢状态。

关键词: 高脂喂养, 棕色脂肪组织, 促红细胞生成素, 含PR结构域蛋白16, 磷酸化信号转导与转录激活因子3, 成纤维细胞生长因子21

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, P< 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.Conclusion: 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.

Key words: high fat diet, brown adipose tissue, erythropoietin, PR domain containing 16, phosphorylated signal transducer and activator of transcription 3, fibroblast growth factor 21

张睿, 陈璐, 葛俊美, 马根山, 蔡君艳. EPO对高脂喂养小鼠棕色脂肪组织PRDM16、FGF21表达及STAT3磷酸化水平的影响[J]. 中国应用生理学杂志, 2018, 34(4): 294-298.

ZHANG Rui, CHEN Lu, GE Jun-mei, MA Gen-shan, CAI Jun-yan. Effect of EPO on PRDM16, FGF21 expression and STAT phosphorylation of brown adipose tissue in HFD mice[J]. CJAP, 2018, 34(4): 294-298.

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EPO对高脂喂养小鼠棕色脂肪组织PRDM16、FGF21表达及STAT3磷酸化水平的影响

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

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