Abbott Caroline R, Kennedy Adam R, Wren Alison M, Rossi Michela, Murphy Kevin G, Seal Leighton J, Todd Jeannie F, Ghatei Mohammad A, Small Caroline J, Bloom Stephen R
Endocrine Unit, Imperial College London, Hammersmith Campus, London W12 ONN, United Kingdom.
Endocrinology. 2003 Sep;144(9):3943-9. doi: 10.1210/en.2003-0149.
The hypothalamic neuropeptide melanin-concentrating hormone (MCH) increases feeding when injected intracerebroventricularly in rats. To identify the hypothalamic nuclei responsible for the orexigenic effect, we injected the peptide into discrete hypothalamic nuclei known to express the MCH receptor, MCH1R. MCH (0.6 nmol) elicited a rapid and significant increase in feeding in satiated rats following injection into the arcuate nucleus (0-1 h: 421 +/- 60%; P < 0.01). An elevation in feeding was also observed following injection into the paraventricular nucleus, which was sustained up to 4 h post injection (0-4 h: 218 +/- 29%; P < 0.01). A significant increase in feeding during this time period was also observed following injection into the dorsomedial nucleus (0-4 h: 155 +/- 12%; P < 0.05). No significant alteration in feeding was observed following injection into the supraoptic nucleus, lateral hypothalamic area, medial preoptic area, anterior hypothalamic area, or ventromedial nucleus of the hypothalamus. To identify the neurotransmitters that may be potentially involved in this effect, we examined their release from hypothalamic explants in vitro following exogenous MCH administration. MCH (1 micro M) increased the release of the orexigenic neurotransmitters neuropeptide Y (37.8 +/- 6.0 fmol/explant vs. basal 30.2 +/- 4.3 fmol/explant; P < 0.05) and agouti-related peptide (4.1 +/- 0.6 fmol/explant vs. basal 2.4 +/- 0.2 fmol/explant; P < 0.05) and decreased the release of the anorectic neurotransmitters alpha-MSH (41.7 +/- 6.8 fmol/explant vs. basal 65.9 +/- 11.0 fmol/explant; P < 0.01) and cocaine- and amphetamine-regulated transcript (112.3 +/- 12.4 fmol/explant vs. basal 167.4 +/- 13.0 fmol/explant; P < 0.001). These studies suggest that the orexigenic effect of MCH may be mediated via activation or inhibition of these feeding circuits within the arcuate nucleus and paraventricular nucleus of the hypothalamus.
下丘脑神经肽黑色素聚集激素（MCH）经脑室内注射到大鼠体内时会增加摄食量。为了确定负责这种促食欲作用的下丘脑核团，我们将该肽注射到已知表达MCH受体MCH1R的离散下丘脑核团中。给饱足的大鼠的弓状核注射MCH（0.6 nmol）后，摄食量迅速且显著增加（0 - 1小时：421±60%；P < 0.01）。向室旁核注射后也观察到摄食量增加，注射后4小时内一直持续（0 - 4小时：|218±29%；P < 0.01）。向背内侧核注射后，在此时间段内摄食量也显著增加（0 - 4小时：155±12%；P < 0.05）。向视上核、下丘脑外侧区、视前内侧区、下丘脑前区或下丘脑腹内侧核注射后，未观察到摄食量有显著变化。为了确定可能参与这种作用的神经递质，我们在体外给予外源性MCH后，检测了下丘脑外植体中它们的释放情况。MCH（1 μM）增加了促食欲神经递质神经肽Y（37.8±6.0 fmol/外植体，基础值为30.2±4.3 fmol/外植体；P < 0.05）和刺鼠相关肽（4.1±0.6 fmol/外植体，基础值为2.4±0.2 fmol/外植体；P < 0.05）的释放，并减少了抑食欲神经递质α - MSH（41.7±6.8 fmol/外植体，基础值为65.9±11.0 fmol/外植体；P < 0.01）和可卡因及苯丙胺调节转录物（112.3±12.4 fmol/外植体，基础值为167.4±13.0 fmol/外植体；P < 0.001）的释放。这些研究表明，MCH的促食欲作用可能通过激活或抑制下丘脑弓状核和室旁核内的这些进食回路来介导。
