Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats
Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats
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DOI：
10.1210/en.2004-0129
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发表时间：
2004-07-01
期刊：
影响因子：
4.8
通讯作者：
Di Carlo, R
中科院分区：
文献类型：
--
作者：
Meli, R;Pacilio, M;Di Carlo, R
绝经后雌激素水平下降导致的肥胖会增加患心脏病、糖尿病和高血压的风险。大鼠卵巢切除术（OVX）是一种很好的雌激素缺乏模型。随之而来的轻度肥胖对研究低雌激素血症如何改变肥胖是有用的。本研究探讨了在卵巢切除（OVX）大鼠雌激素水平的修改或治疗与选择性雌激素受体调节剂，雷洛昔芬（RAL），改变瘦素血症和调节瘦素受体（Ob-R）的丰度在下丘脑和白色脂肪组织，类似于低雌激素诱导的脂肪状态的修改的假设。进行了中期和长期研究（7和22周），以监测大鼠在OVX导致雌激素丢失后以及在用17 β-雌二醇（OVX+E-2）或RAL治疗（OVX+RAL）替代雌激素后瘦素血症的变化。瘦素在OVX大鼠中显著高于对照组，呈时间依赖性。E2和RAL治疗7 wk（P < 0.05）和22 wk（P < 0.001）可逆转上述作用。此外，E-2或RAL治疗逆转了OVX诱导的食物摄入量、体重和脂肪质量含量的增加;检查血清参数的变化以评估不同的脂质谱。我们还评估了Ob-R在下丘脑和脂肪组织中的表达通过Western印迹分析。长的功能亚型（OB-Rb）的表达增加，在7周仅在脂肪组织和减少在22周OVX大鼠在这两个组织中，这些影响被逆转E-2或RAL治疗。我们提供的证据表明，中央和外周OB-Rb的表达与雌激素水平的修改。
Obesity, from declining estrogen levels after menopause, increases the risk of heart disease, diabetes, and hypertension. Ovariectomy (OVX) in rats is a good model of estrogen insufficiency. The ensuing mild obesity is useful to study how hypoestrogenism alters adiposity. This study examines the hypothesis that in ovariectomized (OVX) rats modification of estrogen levels or treatment with a selective estrogen receptor modulator, raloxifene (RAL), alters leptinemia and modulates leptin receptor (Ob-R) abundance in hypothalamus and white adipose tissue, similar to the modification of adipose status induced by hypoestrogenism. Mid- and long-term studies (7 and 22 wk) were conducted to monitor the change in leptinemia in rats after estrogen loss by OVX and after estrogen replacement by 17 beta-estradiol (OVX+E-2) or RAL treatment (OVX+RAL). Leptin was significantly higher in OVX rats vs. controls, in a time-dependent manner. This effect was reversed by both E-2 and RAL treatment at 7 wk (P < 0.05) and 22 wk (P < 0.001). Moreover, E-2 or RAL treatment reversed the OVX-induced increases in food intake, body weight, and fat mass content; the modifications of serum parameters were examined to evaluate the different lipid profiles. We also evaluated Ob-R expression in hypothalamus and adipose tissue by Western blot analysis. The expression of the long functional isoform (Ob-Rb) increased at 7 wk only in adipose tissue and decreased at 22 wk in OVX rats in both tissues; these effects were reversed by E-2 or RAL treatment. We provide evidence that central and peripheral Ob-Rb expression is related to modification of estrogen levels.