Genetic variance contributes to ingestive processes: A survey of 2-deoxy-D-glucose-induced feeding in eleven inbred mouse strains
Genetic variance contributes to ingestive processes: A survey of 2-deoxy-D-glucose-induced feeding in eleven inbred mouse strains
复制标题
DOI：
10.1016/j.physbeh.2005.12.002
复制
发表时间：
2006-03-30
影响因子：
2.9
通讯作者：
Bodnar, RJ
中科院分区：
文献类型：
--
作者：
Lewis, SR;Ahmed, S;Bodnar, RJ
抗代谢葡萄糖类似物2-脱氧-d -葡萄糖（2DG）给药后的摄食反应被概念化为葡萄糖化的实验模型，这可能有助于理解葡萄糖和碳水化合物摄入的个体差异，并最终导致肥胖。虽然已知几种营养素以及食物和水的摄入量的变化与遗传变异有关，但尚不清楚2dg诱导的喂养是否同样依赖于基因型。因此，本研究对11种近交系（A/J、AKR/J、BALB/cJ、CBA/J、C3H/HeJ、C57BL6/J、C57BL10/J、DBA/2J、SJL/J、SWR/J、129P3/J）小鼠和1种近交系（CD-1）小鼠进行了2dg诱导喂养试验，试验范围为先前确定的有效2-DG剂量（200、400、600、800 mg/kg）和试验时间（1-4 h）。在远交系CD-1和近交系DBA/2J小鼠中，在所有四种剂量后，2dg诱导的摄食出现了有序的剂量依赖性增加，在BALB/eJ、SJL/J和129P3/J小鼠中出现了三个最高剂量，在CBA/J和AKR/J小鼠中出现了两个最高剂量。仅在A/J和C3H/HeJ小鼠中观察到最高剂量的2dg诱导喂养，或在C57BL/6J小鼠中观察到中等剂量的2dg诱导喂养。此外，整个2DG剂量范围未能改变C57BL/10J小鼠的食物摄取量，而使SWR/J小鼠的食物摄取量显著减少。在2DG剂量为200-600 mg/kg而不是800 mg/kg时，食物摄入量显示出显著的相互关联，表明大剂量2DG可能对食物摄入产生非特异性效应。在没有（车辆基线）2DG的情况下和存在2DG的情况下，食物摄入量之间没有相关性，这表明未激发小鼠葡萄糖摄入量的调节并不能预测随后对葡萄糖刺激的反应。这些数据证明了这种葡糖酸反应的基因型依赖性变异性，并可能为随后鉴定性状相关基因提供基础。(c) 2006爱思唯尔公司版权所有。
The feeding response following administration of the anti-metabolic glucose analogue, 2-deoxy-D-glucose (2DG), is conceptualized as an experimental model of glucoprivation, which may contribute to the understanding of inter-individual differences in glucose and carbohydrate intake and, ultimately, obesity. Although variation in the intake of several nutrients as well as food and water are known to be associated with genetic variation, it is not known whether 2DG-induced feeding is similarly genotype dependent. The present study therefore examined 2DG-induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) strains across a wide range of previously determined effective 2-DG doses (200, 400, 600, 800 mg/kg) and test times (1-4 h). Orderly dose-dependent increases in 2DG-induced feeding occurred after all four doses in outbred CD-1 and inbred DBA/2J mice, across the three highest doses for BALB/eJ, SJL/J and 129P3/J mice, and across the two highest doses for CBA/J and AKR/J mice. Limited instances of 2DG-induced feeding were noted only at the highest dose in A/J and C3H/HeJ mice, or at a moderate dose in C57BL/6J mice. Further, the full 2DG dose range failed to alter food intake in C57BL/10J mice, and produced significant reductions in food intake in SWR/J mice. Food intake after 2DG doses of 200-600 mg/kg, but not 800 mg/kg, displayed significant cross-correlation, suggesting that large 2DG doses may recruit nonspecific effects upon food intake. There was no correlation between food intake in the absence (vehicle baseline) of and presence of 2DG, suggesting that the regulation of glucose intake in non-challenged mice does not predict subsequent responses to glucoprivic challenge. The data demonstrate genotype-dependent variability in this glucoprivic response, and may provide the basis for the subsequent identification of trait-relevant genes. (c) 2006 Elsevier Inc. All rights reserved.