Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice
Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice
复制标题
DOI：
10.2337/diabetes.45.7.909
复制
发表时间：
1996-07-01
期刊：
影响因子：
7.7
通讯作者：
Flier, JS
中科院分区：
文献类型：
--
作者：
Mantzoros, CS;Qu, DQ;Flier, JS
为了检查瘦素和 β(3) 肾上腺素能系统在食物摄入调节中的潜在相互作用，我们确定了选择性 β(3) 肾上腺素能受体 (AR) 激动剂 (CL 316,243 [1 mg/kg]) 治疗对体重、食物摄入和瘦素表达的影响。研究在 C57Bl/6J 和 FVB 雄性对照小鼠以及定向破坏 β(3) AR 基因的小鼠中进行。这些发现与下丘脑神经肽 Y (NPY) 和黑色素浓缩激素 (MCH) 表达的测量相关，这两种神经肽可能参与食物摄入的中枢调节。在正常动物中，用 CL 316,243 (1 mg/kg) 治疗 12 或 24 小时，瘦素 mRNA 丰度和循环水平降低至基线的 20%。在靶向破坏 beta(3) AR 基因的小鼠中，未观察到 CL 316,243 化合物的作用。尽管瘦素水平下降，β(3) 激动剂的给药仍严重抑制了食物摄入。最后，尽管促食欲神经肽 NPY 和 MCH 的下丘脑表达不变或增加，但食物摄入和瘦素水平的诱导抑制仍然发生。因此，β(3) AR 激动剂通过 β(3) AR 急剧抑制瘦素水平，同时通过瘦素及其两个假定的中心靶标下游的机制抑制食物摄入。
To examine potential interactions between leptin and the beta(3) adrenergic system in the regulation of food intake, we determined the effects of treatment with a selective beta(3) adrenergic receptor (AR) agonist (CL 316,243 [1 mg/kg]) on body weight, food intake, and leptin expression. Studies were carried out in C57Bl/6J and FVB male control mice as well as in mice with targeted disruption of the beta(3) AR gene. These findings were correlated with measurement of the expression in hypothalamus of neuropeptide Y (NPY) and melanin concentrating hormone (MCH), two neuropeptides that may be involved in the central regulation of food intake. Treatment with CL 316,243 (1 mg/kg) for 12 or 24 h decreased leptin mRNA abundance and circulating levels to 20% of baseline in normal animals. No effect of the CL 316,243 compound was seen in mice with targeted disruption of the beta(3) AR gene. Despite the falling leptin levels, beta(3) agonist administration acutely suppressed food intake. Finally, the induced suppression of food intake and leptin levels occurred despite unchanged or increased hypothalamic expression of the orexigenic neuropeptides NPY and MCH. Thus, beta(3) AR agonists via beta(3) ARs suppress leptin levels acutely and simultaneously suppress food intake via a mechanism that operates downstream of leptin and two of its putative central targets.