Mantzoros C S, Qu D, Frederich R C, Susulic V S, Lowell B B, Maratos-Flier E, Flier J S
Division of Endocrinology, Beth Israel Hospital, Boston, Massachusetts, USA.
Diabetes. 1996 Jul;45(7):909-14. doi: 10.2337/diab.45.7.909.
To examine potential interactions between leptin and the beta3 adrenergic system in the regulation of food intake, we determined the effects of treatment with a selective beta3 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 beta3 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 beta3 AR gene. Despite the failing leptin levels, beta3 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, beta3 AR agonists via beta3 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.
为研究瘦素与β3肾上腺素能系统在食物摄入调节中的潜在相互作用，我们测定了用选择性β3肾上腺素能受体（AR）激动剂（CL 316,243 [1毫克/千克]）处理对体重、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β3 AR基因靶向敲除的小鼠中进行。这些发现与神经肽Y（NPY）和促黑素激素（MCH）在下丘脑表达的测量结果相关，这两种神经肽可能参与食物摄入的中枢调节。用CL 316,243（1毫克/千克）处理12或24小时可使正常动物的瘦素mRNA丰度和循环水平降至基线的20%。在β3 AR基因靶向敲除的小鼠中未观察到CL 316,243化合物的作用。尽管瘦素水平下降，但给予β3激动剂可急性抑制食物摄入。最后，尽管促食欲神经肽NPY和MCH在下丘脑的表达未改变或增加，但仍诱导了食物摄入和瘦素水平的抑制。因此，β3 AR激动剂通过β3 ARs可急性抑制瘦素水平，并通过一种在瘦素及其两个假定的中枢靶点下游起作用的机制同时抑制食物摄入。
