Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice
Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice
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DOI：
10.1152/ajpendo.90248.2008
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发表时间：
2008-10-01
影响因子：
5.1
通讯作者：
Dahlman-Wright, Karin
中科院分区：
文献类型：
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作者：
Bryzgalova, Galyna;Lundholm, Lovisa;Dahlman-Wright, Karin
高脂饮食（HFD）喂养的小鼠是肥胖、糖耐量受损和胰岛素抵抗的模型。本研究的主要目的是阐明 17 β-雌二醇 (E2) 在此小鼠模型中抗糖尿病和减肥作用的分子机制。 C57BL/6 雌性小鼠（8 周龄）用 HFD 喂养 10 个月。在喂养的最后一个月每天给予E-2（50μg/kg sc），可降低体重并显着改善葡萄糖耐量和胰岛素敏感性。胰岛素、瘦素、抵抗素和脂联素的血浆水平降低。我们证明，E2 处理降低了白色脂肪组织 (WAT) 中编码抵抗素和瘦素的基因的表达，而脂联素表达则没有变化。此外，在 WAT 中，我们证明甾醇调节元件结合蛋白 1c (SREBP1c) 及其脂肪生成靶基因（如脂肪酸合酶和硬脂酰辅酶 A 去饱和酶 1 (SCD1)）的表达水平降低。在肝脏中，E2处理没有改变肝脏X受体α和SREBP1c等转录因子的表达水平，但关键的脂肪生成基因SCD1的表达降低。这伴随着肝脏甘油三酯含量的降低。重要的是，E2 降低了葡萄糖 6 磷酸酶 (G-6-Pase) 的肝脏表达。我们得出结论，E2 治疗对 HFD 小鼠具有抗糖尿病和抗肥胖作用，并表明这与 WAT 和肝脏中脂肪生成基因的表达减少以及 G-6-Pase 的肝脏表达抑制有关。血浆抵抗素水平降低也可能在这方面发挥重要作用。
The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17 beta-estradiol (E2) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E-2, given daily (50 mu g/kg sc) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E2 treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor alpha and SREBP1c were not changed by E2 treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E2 decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E2 treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.