Swithers S E
Department of Psychological Sciences, Purdue University, West Lafayette, IN 47907-1364, USA.
Appetite. 2000 Aug;35(1):9-25. doi: 10.1006/appe.2000.0330.
We have previously demonstrated that administration of 2-Mercaptoacetate (MA) stimulates independent intake after 1 h in 12 and 15-day-old rat pups, but not younger pups. MA also produces decreases in beta-HBA levels, consistent with the development of a role of altered fatty acid oxidation in modulating independent ingestion in rat pups by 12 days of age. The present experiments extended investigations of the role of changes in energy utilization in young rats by investigating the duration of the effects of altered fatty acid oxidation and the effects of combined blockade of fatty acid oxidation and glucose utilization. Pups were tested at 9, 12 or 15 days of age 3 or 6 h following administration of a dose of 0, 11.4, 22.8, 45.6 or 91.2 mg/kg MA. In pups aged 12 and 15 days, moderate doses of MA stimulated intake 3 h, but not 6 h, following administration. Administration of the highest dose of MA produced significant decreases in beta-HBA levels in pups at all ages when tested after 3 h, but not after 6 h. In the second set of experiments, behavioral and physiological responses to administration of MA (0, 11.4 or 22.8 mg/kg) combined with 2-Deoxyglucose (2-DG: 0, 100 or 200 mg/kg) were investigated in pups aged 6, 9, 12 or 15 days of age. The results demonstrated that while administration of 2-DG produced physiological responses, intake was not stimulated at any age by 2-DG alone or in combination with MA. In fact, in 12 and 15-day-old pups, administration of 2-DG blocked the stimulatory effects of administration of MA. Therefore, while altered utilization of glucose does not appear to be an effective stimulus for increased independent ingestion in pups at this age, altered fatty acid oxidation may be an early metabolic modulator of intake.
我们之前已经证明,给12日龄和15日龄的幼鼠注射巯基乙酸盐(MA)1小时后会刺激其自主摄食,但对更小的幼鼠则无此作用。MA还会使β-羟基丁酸盐(beta-HBA)水平降低,这与到12日龄时脂肪酸氧化改变在调节幼鼠自主摄食中发挥作用的发育过程一致。本实验通过研究脂肪酸氧化改变的影响持续时间以及脂肪酸氧化和葡萄糖利用联合阻断的影响,扩展了对幼鼠能量利用变化作用的研究。给幼鼠注射0、11.4、22.8、45.6或91.2 mg/kg的MA后分别在3或6小时对9、12或15日龄的幼鼠进行测试。在12日龄和15日龄的幼鼠中,中等剂量的MA在给药后3小时而非6小时刺激摄食。在给药3小时后测试时,最高剂量的MA使所有年龄段幼鼠的beta-HBA水平显著降低,但在6小时后测试时则无此作用。在第二组实验中,对6、9、12或15日龄的幼鼠注射MA(0、11.4或22.8 mg/kg)与2-脱氧葡萄糖(2-DG:0、100或200 mg/kg)组合后的行为和生理反应进行了研究。结果表明,虽然注射2-DG会产生生理反应,但单独使用2-DG或与MA联合使用时在任何年龄段都不会刺激摄食。事实上,在12日龄和15日龄的幼鼠中,注射2-DG会阻断MA给药的刺激作用。因此,虽然葡萄糖利用改变似乎不是这个年龄段幼鼠增加自主摄食的有效刺激因素,但脂肪酸氧化改变可能是摄食的早期代谢调节因子。