Metaformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance
Metaformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance
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DOI：
10.2337/diabetes.55.03.06.db05-0917
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发表时间：
2006-03-01
期刊：
影响因子：
7.7
通讯作者：
Moon, KH
中科院分区：
文献类型：
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作者：
Kim, YW;Kim, JY;Moon, KH
为了评估二甲双胍是否增强瘦素敏感性，我们在标准饲料和高脂肪喂养的肥胖大鼠中测量了二甲双胍治疗4周（每日300 mg/kg）后的瘦素敏感性。二甲双胍治疗增强了标准饲料大鼠脑室内输注瘦素7天（每只大鼠每天15 μ g）后的厌食和减脂反应，与年龄匹配的标准饲料大鼠相比，高脂喂养的肥胖大鼠对瘦素的这些反应减弱。然而，这些反应瘦纠正二甲双胍治疗高脂肪喂养的肥胖大鼠。此外，二甲双胍治疗的标准饲料和高脂喂养的肥胖大鼠血清瘦素和胰岛素浓度显着下降。二甲双胍治疗组大鼠下丘脑磷酸化AMP活化蛋白激酶水平较未治疗组降低。在一项急性研究中，二甲双胍治疗也增加了瘦素（5 μ g）的抗肿瘤作用，并伴随着下丘脑中磷酸化信号转导子和转录激活子3水平的增加。这些结果表明，二甲双胍提高瘦素敏感性和纠正瘦素抵抗高脂肪喂养的肥胖大鼠和联合治疗，包括二甲双胍和瘦素将有助于治疗肥胖。
To evaluate whether metformin enhances leptin sensitivity, we measured leptin sensitivity after 4 weeks of metformin treatment (300 mg/kg daily) in both standard chow and high-fat-fed obese rats. Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 mu g daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat-fed obese rats compared with age-matched standard chow rats. However, these responses to leptin were corrected by metformin treatment in high-fat-fed obese rats. Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat-fed obese rats. The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats. In an acute study, metformin treatment also increased the anorexic effect of leptin (5 mu g), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus. These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat-fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.