DIABETOLOGIA:多碘营养素的缺失改变了小鼠体内的葡萄糖稳态、能量代谢和棕色脂肪的生热功能

2019-04-04 不详 网络

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多效磷是一种高度保守的细胞因子,具有调节细胞生长和生存等多种功能。在此,我们假设这种细胞因子可以在糖和脂质平衡中发挥调节作用。

为了验证这一假设,我们进行了一项纵向研究,描述了基因靶向ptn缺陷雌性小鼠及其对应的野生型小鼠在不同年龄阶段的代谢谱(循环变量和组织mRNA表达),从青年期(3个月)到老年期(15个月)。采用代谢笼研究24℃和30℃下呼吸交换率和能量消耗。未分化使小鼠棕色脂肪细胞(mBA)处理0.1μg /毫升pleiotrophin直到天6的区别,和标记的mBA分化进行定量实时PCR (qPCR)分析。

结果显示,Ptn的缺失与全身脂肪总量的减少(Ptn+/+20.2%Ptn−/−13.9%)和分离的15个月大的小鼠脂肪细胞对异丙肾上腺素的脂解反应增强(Ptn+/+189%Ptn−/−273%)有关。我们发现Ptn−/−小鼠的QUICKI值显著降低,脂质谱发生改变;血浆三酰甘油和NEFA不像Ptn+/+小鼠那样随着年龄增长而增加。此外,Ptn−/−小鼠的冷诱导产热对能量消耗的贡献大于Ptn+/+小鼠(分别为42.6%33.6%)。在Ptn−/−小鼠棕色脂肪组织中,体温、脱碘酶、T3和线粒体解偶联蛋白-1的活性和表达均高于野生型对照组。最后,布朗pre-adipocytes pleiotrophin棕色脂肪细胞标记物的表达使Cidea(减少20%),Prdm16(减少21%),Pgc1-α(也称为Ppargc1a减少11%)下降。

我们的研究结果首次揭示了多效磷在维持胰岛素敏感性、促进脂肪组织脂质代谢和可塑性、调节能量代谢和产热等方面起着关键作用。这些发现为治疗代谢紊乱开辟了治疗途径。

原始出处:

Julio SevillanoMaría Gracia Sánchez-Alonso, Pleiotrophin deletion alters glucose homeostasis, energy metabolism and brown fat thermogenic function in mice

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    2019-06-01 changfy
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