Rossi M, Choi S J, O'Shea D, Miyoshi T, Ghatei M A, Bloom S R
Division of Endocrinology and Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Endocrinology. 1997 Jan;138(1):351-5. doi: 10.1210/endo.138.1.4887.
Melanin-concentrating hormone (MCH) has recently been proposed as both a central stimulator and an inhibitor of food intake. To clarify its role, we investigated the effects of MCH and the prepro-MCH-derived peptide neuropeptide E-I injected intracerebroventricularly (icv) in rats. MCH (0.15-15 micrograms) was injected icv at the beginning of the light phase. Food intake at 2 h showed a dose-dependent increase from 325 +/- 7% of the control value (1.5-microgram dose; P < 0.05) to 462 +/- 30% of the control value (15-microgram dose; P < 0.005). When 10 ng, 100 ng, and 5 micrograms MCH were injected icv at the beginning of the dark phase, only 5 micrograms stimulated feeding (166 +/- 16% of the control value; P < 0.05). At no dose did MCH inhibit feeding. Twice daily icv injections of MCH (5 micrograms) caused an average 197 +/- 9% increase in 2-h food intake for the first 5 days. Injections from days 6-8 did not stimulate feeding. Food intake and body weight at 24 h remained unchanged. Intracerebroventricular neuropeptide E-I had no effect on food intake alone and did not alter MCH-induced feeding. These studies show a dose-dependent stimulation of feeding by acute central administration of MCH. Tolerance is seen with chronic administration. These findings support a role for MCH in the immediate regulation of food intake, but not in body weight control.
黑色素浓缩激素(MCH)最近被认为既是食物摄入的中枢刺激物,也是抑制剂。为了阐明其作用,我们研究了脑室注射(icv)MCH和前pro-MCH衍生肽神经肽E-I对大鼠的影响。在光照期开始时icv注射MCH(0.15 - 15微克)。2小时后的食物摄入量呈剂量依赖性增加,从对照值的325±7%(1.5微克剂量;P < 0.05)增加到对照值的462±30%(15微克剂量;P < 0.005)。当在黑暗期开始时icv注射10纳克、100纳克和5微克MCH时,只有5微克刺激进食(为对照值的166±16%;P < 0.05)。在任何剂量下MCH均未抑制进食。每天两次icv注射MCH(5微克)在前5天导致平均2小时食物摄入量增加197±9%。第6 - 8天的注射未刺激进食。24小时的食物摄入量和体重保持不变。脑室注射神经肽E-I单独对食物摄入量没有影响,也不改变MCH诱导的进食。这些研究表明急性中枢给予MCH会对进食产生剂量依赖性刺激。慢性给药会出现耐受性。这些发现支持MCH在食物摄入的即时调节中起作用,但在体重控制中不起作用。