Melanin-concentrating hormone receptor 1 deficiency increases insulin sensitivity in obese leptin-deficient mice without affecting body weight
Melanin-concentrating hormone receptor 1 deficiency increases insulin sensitivity in obese leptin-deficient mice without affecting body weight
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DOI：
10.2337/diabetes.55.03.06.db05-1302
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发表时间：
2006-03-01
期刊：
影响因子：
7.7
通讯作者：
Bohlooly-Y, M
中科院分区：
文献类型：
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作者：
Bjursell, M;Gerdin, AK;Bohlooly-Y, M
下丘脑肽黑色素浓集激素（MCH）在能量稳态中起重要作用。过度表达MCH的动物会出现食欲过盛、肥胖和胰岛素抵抗。在这项研究中，小鼠缺乏MCH受体-1（MCHr 1敲除）和瘦素（ob/ob）双无效小鼠（MCHr 1敲除ob/ob），以研究肥胖和/或胰岛素抵抗与肥胖表型的ob/ob小鼠是否通过消融MCHr 1基因而减弱。在MCHr 1基因敲除ob/ob小鼠中，尽管在体重、食物摄入或能量消耗方面没有差异，但与ob/ob小鼠相比，口服葡萄糖负荷导致较低的血糖反应和显著较低的胰岛素水平。此外，与ob/ob小鼠相比，MCHr 1基因敲除ob/ob小鼠具有更高的运动活性和瘦体重，更低的体脂量，以及改变的体温调节。总之，MCHr 1通过不依赖于体重减轻的机制对胰岛素敏感性和/或分泌很重要。
The hypothalamic peptide melanin-concentrating hormone (MCH) plays important roles in energy homeostasis. Animals overexpressing MCH develop hyperphagia, obesity, and insulin resistance. In this study, mice lacking both the MCH receptor-1 (MCHr1 knockout) and leptin (ob/ob) double-null mice (MCHr1 knockout ob/ob) were generated to investigate whether the obesity and/or the insulin resistance linked to the obese phenotype of ob/ob mice was attenuated by ablation of the MCHr1 gene. In MCHr1 knockout ob/ob mice an oral glucose load resulted in a lower blood glucose response and markedly lower insulin levels compared with the ob/ob mice despite no differences in body weight, food intake, or energy expenditure. In addition, MCHr1 knockout ob/ob mice had higher locomotor activity and lean body mass, lower body fat mass, and altered body temperature regulation compared with ob/ob mice. In conclusion, MCHr1 is important for insulin sensitivity and/or secretion via a mechanism not dependent on decreased body weight.