Specter S E, Horwitz B A, Beverly J L
Department of Nutrition, University of California, Davis 95616, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):R388-92. doi: 10.1152/ajpregu.1996.271.2.R388.
The diminished sensitivity of genetically obese (fa/ fa) Zucker rats to the glucoprivic agent 2-deoxy-D-glucose (2-DG) may involve impaired release of the neurotransmitter gamma-aminobutyric acid (GABA) in discrete regions of the hypothalamus. Extracellular GABA concentrations in the medial (MH) and lateral (LH) hypothalamus of lean (Fa/Fa) and age-matched obese (fa/fa) male Zucker rats before and after 2-DG (1.2 mmol/kg i.v.). Basal GABA concentrations were higher (P < 0.05) in the MH of obese vs. lean rats. No differences were noted in LH GABA levels between lean and obese rats or in baseline extracellular GABA levels between brain regions in lean rats. In lean rats, a characteristic bimodal increase in GABA concentrations was apparent in the MH, whereas GABA concentrations decreased in the LH during the 60 min after 2-DG. No changes in GABA concentrations in dialysate from the MH or LH of obese rats were observed after 2-DG. The alterations in basal activity and responsiveness to glucoprivic stimuli by GABAergic system in the MH of obese rats may reflect a defect in central glucostatic control of food intake and, ultimately, in the hypothesized autonomic imbalance in fa/fa Zucker rat.
遗传性肥胖（fa/fa）的 Zucker 大鼠对糖缺乏剂 2-脱氧-D-葡萄糖（2-DG）的敏感性降低，可能与下丘脑离散区域神经递质γ-氨基丁酸（GABA）释放受损有关。静脉注射 2-DG（1.2 mmol/kg）前后，瘦型（Fa/Fa）和年龄匹配的肥胖型（fa/fa）雄性 Zucker 大鼠下丘脑内侧（MH）和外侧（LH）的细胞外 GABA 浓度。肥胖大鼠 MH 中的基础 GABA 浓度高于瘦型大鼠（P < 0.05）。瘦型和肥胖大鼠 LH 中的 GABA 水平以及瘦型大鼠不同脑区的基线细胞外 GABA 水平均无差异。在瘦型大鼠中，MH 中 GABA 浓度呈现出典型的双峰增加，而在 2-DG 注射后的 60 分钟内，LH 中的 GABA 浓度降低。2-DG 注射后，未观察到肥胖大鼠 MH 或 LH 透析液中 GABA 浓度的变化。肥胖大鼠 MH 中 GABA 能系统的基础活性和对糖缺乏刺激的反应性改变，可能反映了中枢对食物摄入的糖稳态控制缺陷，最终反映了 fa/fa Zucker 大鼠假设的自主神经失衡。
