Lemierre S, Rouch C, Nicolaidis S, Orosco M
Neurobiologie des Régulations, CNRS UPR 9054, aff. INSERM, Collège de France, Paris.
Int J Obes Relat Metab Disord. 1998 Oct;22(10):993-9. doi: 10.1038/sj.ijo.0800717.
The obesity of the Zucker rat is associated with numerous metabolic and neurochemical disturbances involving the central transmitters regulating feeding behaviour. Among them, the release of satiety-related monoamines from the median hypothalamus in response to a meal is enhanced in obese, as compared to normal, rats as though larger amounts of these amines were necessary to bring about satiety in obese rats. Besides, the obese Zucker rat has often been described as shorter-living than its lean congener. One of the reasons for the shorter longevity of the obese rat was investigated in this study: it could be an aggravation of its obesity-related central disturbances with age.
We assessed the response to a meal of the hypothalamic monoamines, dopamine and serotonin, in young (four month old) and old (twelve month old) lean (Fa-Fa) and obese (fa-fa) Zucker rats. The in vivo technique of microdialysis was used to combine behavioural recordings and continuous neurochemical assays.
The exacerbation of monoamine release observed in young obese rats in response to a meal was no longer found in old obese rats. Serotonin increase during a meal weakened with aging, especially in obese rats. Dopamine (DA) response to a meal was completely reversed in old obese rats, with a decrease instead of the increase observed in the three other groups.
The decrease of monoaminergic response to a meal with age is apparently the opposite to the enhanced release related to obesity. However, this does not correspond to an amelioration of the hyperphagia of the obese rats with age, as we could observe in parallel behavioural experiments, but rather to a decrease in neurotransmitter metabolism and thus in neuronal functioning.
Zucker大鼠的肥胖与众多代谢和神经化学紊乱有关，这些紊乱涉及调节进食行为的中枢递质。其中，与正常大鼠相比，肥胖大鼠在进食后下丘脑中部与饱腹感相关的单胺释放增强，就好像需要更多量的这些胺才能使肥胖大鼠产生饱腹感。此外，肥胖的Zucker大鼠通常被描述为比其瘦的同类寿命短。本研究调查了肥胖大鼠寿命较短的原因之一：可能是其与肥胖相关的中枢紊乱随年龄加剧。
我们评估了年轻（4个月大）和年老（12个月大）的瘦型（Fa-Fa）和肥胖型（fa-fa）Zucker大鼠进食后下丘脑单胺、多巴胺和5-羟色胺的反应。采用微透析体内技术结合行为记录和连续神经化学分析。
在年老肥胖大鼠中未发现年轻肥胖大鼠进食后单胺释放加剧的情况。进食期间5-羟色胺的增加随衰老而减弱，尤其是在肥胖大鼠中。年老肥胖大鼠进食后多巴胺（DA）反应完全逆转，出现下降，而其他三组则是升高。
随着年龄增长，对进食的单胺能反应降低显然与肥胖相关的释放增强相反。然而，正如我们在平行行为实验中观察到的，这并不对应于肥胖大鼠随着年龄增长贪食情况的改善，而是对应于神经递质代谢的降低，进而神经元功能的降低。
