Meal-induced changes in extracellular 5-HT in medial hypothalamus of lean (Fa/Fa) and obese (fa/fa) Zucker rats
Meal-induced changes in extracellular 5-HT in medial hypothalamus of lean (Fa/Fa) and obese (fa/fa) Zucker rats
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DOI：
10.1016/s0006-8993(01)02371-x
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发表时间：
2001-06-01
期刊：
影响因子：
2.9
通讯作者：
Horwitz, BA
中科院分区：
文献类型：
--
作者：
De Fanti, BA;Hamilton, JS;Horwitz, BA
下丘脑5-羟色胺(5-MT)参与食欲调节和交感神经生热刺激。这项研究验证了一种假设，即肥胖的Zucker大鼠能量效率的提高与内侧下丘脑(MH)5-羟色胺能释放迟钝有关。我们用微透析法和高效液相色谱-电化学法测定了10-13周龄雄性瘦(Fa/Fa)和肥胖(Fa/fa)Zucker大鼠餐前和餐后MH细胞外5-羟色胺(5-HT)水平的动态变化。瘦大鼠和肥胖大鼠之间的基础5-羟色胺水平没有差异。与下丘脑5-羟色胺在进食中起生理作用的说法一致，无论是瘦鼠还是肥胖大鼠，进食后细胞外5-羟色胺水平都显著增加。这种增加是在他们吃8.1千卡热量的20分钟间隔内观察到的，并保持了另外的60分钟。瘦(1.46+/-0.38moll/mul)和肥胖(1.21+/-0.82fmol/mul)大鼠在进餐间隔期间5-羟色胺的净释放量相当。然而，肥胖大鼠的5-羟色胺水平(1.80+/-0.29fmol/mul)在接下来的20分钟内趋于平稳，而肥胖大鼠的5-羟色胺水平(2.74+/-0.53fmol/mul)持续升高，并在餐后40分钟和60分钟显著高于倾斜大鼠。这导致在进餐期间的总净释放量加上随后的三个20分钟间隔，肥胖组(9.83+/-1.16fmol/MU1)显著高于瘦大鼠(5.59+/-0.85fmol/MU1)。因此，肥胖的Zucker大鼠能量效率的提高可能与进食后5-羟色胺释放减弱无关。相反，它们在MH中5-羟色胺的释放增加可能反映了对Orexigen NPY升高的代偿机制、膳食诱导的CCK释放的减少和/或对5-羟色胺的功能性抵抗。(C)2001年由爱思唯尔科学出版。
Hypothalamic serotonin (5-MT) is involved in appetite regulation and sympathetic stimulation of thermogenesis. This study tested the hypothesis that the enhanced energetic efficiency of obese Zucker rats involves blunted serotonergic release within the medial hypothalamus (MH). We used microdialysis and HPLC-EC to measure dynamic changes in extracellular 5-HT levels in the MH of 10-13-week-old male lean (Fa/Fa) and obese (fa/fa) Zucker rats before and after a meal. No differences were noted in basal levels of 5-HT between lean and obese rats. Consistent with the suggestion that hypothalamic 5-HT plays a physiological role in feeding, extracellular 5-HT levels increased significantly in both lean and obese rats given a meal. This increase was observed in the 20 min interval in which they ate the 8.1 kcal meal and remained for an additional 60 min. The net release of 5-HT during the meal interval was comparable in the lean (1.46 +/-0.38 moll/mul) and obese (1.21 +/-0.82 fmol/mul) rats. However, the 5-HT levels of the leans (1.80 +/-0.29 fmol/mul) plateaued in the next 20 min interval, whereas they continued rising (2.74 +/-0.53 fmol/mul) in obese rats and were significantly higher than those in the leans during the 40 and 60 min intervals after the meal was presented. This resulted in a total net release during the meal plus the next three 20 min intervals that was significantly higher in obese (9.83 +/-1.16 fmol/mu1) than in lean (5.59 +/-0.85 fmol/mul) rats. Thus, the enhanced energetic efficiency of the obese Zucker rats may not be associated with attenuated serotonin release in response to a meal. Rather their enhanced release of 5-HT in the MH may reflect compensatory mechanisms for the elevated orexigen NPY, the reduction in meal-induced CCK release, and/or a functional resistance to 5-HT. (C) 2001 Published by Elsevier Science.