De Fanti B A, Hamilton J S, Horwitz B A
Neurobiology, Physiology and Behavior, Division of Biological Sciences, University of California, One Shields Avenue, 95616, Davis, CA, USA.
Brain Res. 2001 Jun 1;902(2):164-70. doi: 10.1016/s0006-8993(01)02371-x.
Hypothalamic serotonin (5-HT) 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 fmol/microl) and obese (1.21+/-0.82 fmol/microl) rats. However, the 5-HT levels of the leans (1.80+/-0.29 fmol/microl) plateaued in the next 20 min interval, whereas they continued rising (2.74+/-0.53 fmol/microl) 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/microl) than in lean (5.59+/-0.85 fmol/microl) 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.
下丘脑5-羟色胺（5-HT）参与食欲调节和产热的交感神经刺激。本研究检验了以下假设：肥胖Zucker大鼠能量效率的提高涉及下丘脑内侧（MH）中5-羟色胺能释放的减弱。我们使用微透析和高效液相色谱-电化学检测法来测量10 - 13周龄雄性瘦型（Fa/Fa）和肥胖型（fa/fa）Zucker大鼠进食前后MH中细胞外5-HT水平的动态变化。瘦型和肥胖型大鼠的5-HT基础水平未发现差异。与下丘脑5-HT在进食中起生理作用的观点一致，给予进食后，瘦型和肥胖型大鼠的细胞外5-HT水平均显著升高。这种升高在它们进食8.1千卡食物的20分钟间隔内观察到，并持续额外60分钟。进食间隔期间5-HT的净释放量在瘦型（1.46±0.38 fmol/μl）和肥胖型（1.21±0.82 fmol/μl）大鼠中相当。然而，瘦型大鼠（1.80±0.29 fmol/μl）的5-HT水平在接下来的20分钟间隔内达到平稳，而肥胖型大鼠的5-HT水平继续上升（2.74±0.53 fmol/μl），并且在进食后40分钟和60分钟间隔内显著高于瘦型大鼠。这导致在进食加上接下来三个20分钟间隔期间的总净释放量，肥胖型大鼠（9.83±1.16 fmol/μl）显著高于瘦型大鼠（5.59±0.85 fmol/μl）。因此，肥胖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-HT释放的增强可能反映了对促食欲神经肽Y升高、进食诱导的胆囊收缩素释放减少和/或对5-HT的功能抗性的补偿机制。
