Orosco M, Rouch C, Gripois D, Blouquit M F, Roffi J, Jacquot C, Cohen Y
Neurobiologie des Régulations, Collège de France, Paris.
Psychoneuroendocrinology. 1992 Oct;17(5):443-52. doi: 10.1016/0306-4530(92)90002-o.
The genetically obese Zucker rat presents several abnormalities related to insulin and brain monoamines, which may play a role in its impaired regulation of food intake and body weight. In a previous study, the possible insulin-monoamine interplay was investigated by measuring brain monoamine and metabolite levels in the three genotypes of the Zucker strain. In addition to the expected results, insulin had a particular effect on striatal dopamine (DA) release, regardless of ponderal status and genotype. We further investigated this point in the present study, using the brain microdialysis technique in the striatum. Lean homozygous Fa-Fa rats responded as expected to insulin with regard to striatal DA release, with increases in DA and 3-methoxy-tyramine levels and decreases in dihydroxyphenylacetic acid and homovanillic acid. Lean heterozygous Fa-fa rats showed a very specific response profile, with decreases in all dopaminergic parameters, suggestive of an effect on DA synthesis rather than DA release. This further emphasizes the marked differences between homozygous and heterozygous lean rats. The obese fa-fa rats clearly fell into two populations. The first showed a profile of response to insulin similar to that of the lean Fa-fa rats, in keeping with the disturbances related to the "fa" gene. The second showed an increase in all the dopaminergic parameters. This pattern of response was, however, different from that of the Fa-Fa rats. These opposing responses in the two obese populations did not reflect differences in the blood glucose response to insulin. One explanation is that 16 wk may be a critical transition period in the development of genetic obesity, with regard to brain monoamine disturbances and the response to insulin.
遗传性肥胖的 Zucker 大鼠存在一些与胰岛素和脑单胺类物质相关的异常情况，这些异常可能在其食物摄入和体重调节受损中发挥作用。在先前的一项研究中，通过测量 Zucker 品系三种基因型大鼠的脑单胺类物质和代谢产物水平，对胰岛素 - 单胺之间可能的相互作用进行了研究。除了预期的结果外，无论体重状况和基因型如何，胰岛素对纹状体多巴胺（DA）释放都有特殊影响。在本研究中，我们使用纹状体脑微透析技术进一步研究了这一点。瘦型纯合 Fa - Fa 大鼠在纹状体 DA 释放方面对胰岛素的反应符合预期，DA 和 3 - 甲氧基酪胺水平升高，二羟基苯乙酸和高香草酸水平降低。瘦型杂合 Fa - fa 大鼠表现出非常特殊的反应模式，所有多巴胺能参数均降低，提示对 DA 合成而非 DA 释放有影响。这进一步强调了纯合和杂合瘦型大鼠之间的显著差异。肥胖的 fa - fa 大鼠明显分为两个群体。第一个群体对胰岛素的反应模式与瘦型 Fa - fa 大鼠相似，这与“fa”基因相关的紊乱情况相符。第二个群体所有多巴胺能参数均升高。然而，这种反应模式与 Fa - Fa 大鼠不同。这两个肥胖群体中的相反反应并不反映血糖对胰岛素反应的差异。一种解释是，就脑单胺紊乱和对胰岛素的反应而言，16 周可能是遗传性肥胖发展过程中的一个关键过渡期。
