Lewis Sarah R, Dym Cheryl, Ginzberg Miriam, Kest Benjamin, Bodnar Richard J
Neuropsychology Doctoral Sub-Program and Department of Psychology, City University of New York, USA.
Physiol Behav. 2006 Jul 30;88(4-5):516-22. doi: 10.1016/j.physbeh.2006.05.003.
The feeding response following administration of the free fatty acid oxidation inhibitor, mercaptoacetate (MA) is conceptualized as an experimental model of lipoprivation, which may contribute to the understanding of inter-individual differences in the modulation of this homeostatic response. Although variation in the intake of food, water and glucoprivation as well as intake of several nutrients is known to be associated with genetic variation, it is not known whether MA-induced feeding is similarly dependent upon genotype. The present study therefore examined MA-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 MA doses (5, 35, 70, 100 mg/kg) and test times (1-4 h). MA produced significant dose-dependent and strain-dependent increases in food intake with strong responses noted in DBA/2J, outbred CD-1 and AKR/J mice. More limited dose-specific increases in food intake following MA occurred in C3H/HeJ, BALB/cJ, CBA/J, SJL/J, SWR/J and C57BL/6J mice. In contrast, MA failed to significantly increase food intake in A/J, C57BL/10J and 129P/3J mice. MA-induced food intake correlated significantly across strains only following the two highest doses, and intake following only the highest MA dose correlated significantly across strains with intake following only a moderate glucoprivic dose of 2-deoxy-d-glucose. Thus, these inter-strain differences suggest that lipoprivic (e.g., MA intake) and glucoprivic (e.g., 2-deoxy-d-glucose intake) responsivity operate via only partially overlapping genetic mechanisms of action. The demonstration of genotype-dependent variability in this lipoprivic response may provide the basis for the subsequent identification of trait-relevant genes.
给予游离脂肪酸氧化抑制剂巯基乙酸盐（MA）后的摄食反应被视为脂肪缺乏的一种实验模型，这可能有助于理解这种稳态反应调节过程中的个体差异。尽管已知食物、水和糖缺乏的摄入量变化以及几种营养素的摄入量与基因变异有关，但尚不清楚MA诱导的摄食是否同样依赖于基因型。因此，本研究检测了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）和一种远交系（CD-1）小鼠在一系列先前确定的有效MA剂量（5、35、70、100 mg/kg）和测试时间（1 - 4小时）下MA诱导的摄食情况。MA导致食物摄入量出现显著的剂量依赖性和品系依赖性增加，在DBA/2J、远交系CD-1和AKR/J小鼠中观察到强烈反应。在C3H/HeJ、BALB/cJ、CBA/J、SJL/J、SWR/J和C57BL/6J小鼠中，MA后食物摄入量的剂量特异性增加较为有限。相比之下，MA未能显著增加A/J、C57BL/10J和129P/3J小鼠的食物摄入量。仅在两个最高剂量后，MA诱导的食物摄入量在各品系间显著相关，并且仅在最高MA剂量后的摄入量与仅在中等糖缺乏剂量2-脱氧-D-葡萄糖后的摄入量在各品系间显著相关。因此，这些品系间差异表明，脂肪缺乏（如MA摄入）和糖缺乏（如2-脱氧-D-葡萄糖摄入）反应性仅通过部分重叠的遗传作用机制发挥作用。这种脂肪缺乏反应中基因型依赖性变异性的证明可能为后续鉴定与性状相关的基因提供基础。
