Modulation of olfactory sensitivity and glucose-sensing by the feeding state in obese Zucker rats.
Modulation of olfactory sensitivity and glucose-sensing by the feeding state in obese Zucker rats.
复制标题
DOI：
10.3389/fnbeh.2014.00326
复制
发表时间：
2014
影响因子：
3
通讯作者：
Julliard AK
中科院分区：
文献类型：
--
作者：
Aimé P;Palouzier-Paulignan B;Salem R;Al Koborssy D;Garcia S;Duchamp C;Romestaing C;Julliard AK
Zucker fa/fa 大鼠已被广泛用作研究肥胖的动物模型，因为它重现了大多数行为和代谢功能障碍，例如食欲过盛、高血糖和胰岛素抵抗。尽管众所周知嗅觉受到营养和激素的影响，但代谢功能障碍对肥胖 Zucker 大鼠嗅觉系统中的嗅觉性能和葡萄糖感应的影响却知之甚少。在本研究中，我们使用基于条件性嗅觉厌恶的行为范式，证明肥胖和瘦的 Zucker 大鼠在禁食时比饱食时具有更好的嗅觉敏感性。有趣的是，肥胖的 Zucker 大鼠比瘦对照大鼠表现出更高的嗅觉敏感性。通过研究嗅觉系统中葡萄糖感应的分子机制，我们证明钠偶联葡萄糖转运蛋白 1 (SGLT1) 和胰岛素依赖性葡萄糖转运蛋白 4 (GLUT4) 均在嗅球 (OB) 中表达。通过比较肥胖和瘦Zucker大鼠OB中GLUT4和SGLT1的表达，我们发现只有SGLT1以基因型依赖性方式受到调节。接下来，我们使用葡萄糖氧化酶生物传感器在体内同时测量 OB 和皮质中的细胞外液葡萄糖浓度 ([Gluc]ECF)。在代谢稳定状态下，我们确定 OB 中的葡萄糖含量是皮质中的两倍。在这两个区域，肥胖大鼠的 [Gluc]ECF 比瘦对照大鼠高 2 倍。在诱导的动态血糖条件下，胰岛素注射使OB中的[Gluc]ECF比皮质中的[Gluc]ECF降低更大。注射葡萄糖不影响 Zucker fa/fa 大鼠的 OB [Gluc]ECF。总之，这些结果强调了葡萄糖对于 OB 网络功能的重要性，并为建立 OB 葡萄糖传感作为感觉嗅觉处理的关键因素提供了强有力的论据。
The Zucker fa/fa rat has been widely used as an animal model to study obesity, since it recapitulates most of its behavioral and metabolic dysfunctions, such as hyperphagia, hyperglycemia and insulin resistance. Although it is well established that olfaction is under nutritional and hormonal influences, little is known about the impact of metabolic dysfunctions on olfactory performances and glucose-sensing in the olfactory system of the obese Zucker rat. In the present study, using a behavioral paradigm based on a conditioned olfactory aversion, we have shown that both obese and lean Zucker rats have a better olfactory sensitivity when they are fasted than when they are satiated. Interestingly, the obese Zucker rats displayed a higher olfactory sensitivity than their lean controls. By investigating the molecular mechanisms involved in glucose-sensing in the olfactory system, we demonstrated that sodium-coupled glucose transporters 1 (SGLT1) and insulin dependent glucose transporters 4 (GLUT4) are both expressed in the olfactory bulb (OB). By comparing the expression of GLUT4 and SGLT1 in OB of obese and lean Zucker rats, we found that only SGLT1 is regulated in genotype-dependent manner. Next, we used glucose oxidase biosensors to simultaneously measure in vivo the extracellular fluid glucose concentrations ([Gluc]ECF) in the OB and the cortex. Under metabolic steady state, we have determined that the OB contained twice the amount of glucose found in the cortex. In both regions, the [Gluc]ECF was 2 fold higher in obese rats compared to their lean controls. Under induced dynamic glycemia conditions, insulin injection produced a greater decrease of [Gluc]ECF in the OB than in the cortex. Glucose injection did not affect OB [Gluc]ECF in Zucker fa/fa rats. In conclusion, these results emphasize the importance of glucose for the OB network function and provide strong arguments towards establishing the OB glucose-sensing as a key factor for sensory olfactory processing.
登录
查看更多内容
影响因子：
3.7
作者：
Aimé P;Hegoburu C;Jaillard T;Degletagne C;Garcia S;Messaoudi B;Thevenet M;Lorsignol A;Duchamp C;Mouly AM;Julliard AK
通讯作者：
Julliard AK
影响因子：
2.5
作者：
Fadool, DA;Tucker, K;Simmen, JA
通讯作者：
Simmen, JA
影响因子：
2.7
作者：
Aime, P.;Duchamp-Viret, P.;Julliard, A. K.
通讯作者：
Julliard, A. K.
影响因子：
5.3
作者：
Chaigneau, Emmanuelle;Tiret, Pascale;Charpak, Serge
通讯作者：
Charpak, Serge
影响因子：
3.8
作者：
Bowlby, MR;Fadool, DA;Levitan, IB
通讯作者：
Levitan, IB