Melanin-concentrating hormone receptor is a target of leptin action in the mouse brain.
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that is important in the regulation of energy homeostasis. MCH signals via a seven-transmembrane G protein-coupled receptor, which is coupled to Galpha(i). This receptor was initially cloned in rat and human and designated SLC-1 because of its homology to the somatostatin receptor. In rat brain, it is expressed in a pattern that mirrors the previously described pattern of projections of MCH-immunoreactive fibers. In the present study we cloned the mouse MCH receptor (MCH-R) ortholog by a rapid amplification of 5'- and 3'-cDNA ends approach and have found it to be 98% homologous with the rat sequence. We have characterized MCH-R messenger RNA distribution in the mouse brain by in situ hybridization and have shown MCH-R to be expressed in diverse brain areas implicated in the regulation of feeding, body adiposity, and sensory integration of smell and gustatory inputs, including the hypothalamus [paraventricular nucleus (magnocellular part) and dorsomedial, ventromedial, and arcuate nucleus], areas of the olfactory pathway, and the nucleus of the solitary tract. We also studied MCH-R regulation and found that MCH-R expression is increased 7-fold by 48-h fasting or genetic leptin deficiency (ob/ob mice) and is completely blunted by leptin administration. In contrast, MCH-R messenger RNA expression remains unaltered in genetic MCH deficiency. Our findings suggest that MCH-R constitutes a central target of leptin action in the mammalian brain.
Kokkotou
E G
EG
Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Tritos
N A
NA
Mastaitis
J W
JW
Slieker
L
L
Maratos-Flier
E
E
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D007028:Hypothalamic Hormones / Q000235:genetics; D020738:Leptin / Q000502:physiology*; D008297:Male; D008543:Melanins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D008969:Molecular Sequence Data; D010907:Pituitary Hormones / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000235:genetics
D018076:DNA, Complementary; D007028:Hypothalamic Hormones; C515448:LEPR protein, human; D020738:Leptin; C491208:MCHR1 protein, rat; C491209:Mchr1 protein, mouse; D008543:Melanins; D010907:Pituitary Hormones; D012333:RNA, Messenger; D054411:Receptors, Leptin; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; C515447:leptin receptor, mouse; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone