Melanin-concentrating hormone receptor is a target of leptin action in themouse 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 G alpha (i). This receptor was initially cloned in rat and human and designated SLC-1 be cause of its homology to the somatostatin receptor. In rat brain, it is exp ressed in a pattern that mirrors the previously described pattern of projec tions 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 messen ger RNA distribution in the mouse brain by in situ hybridization and have s hown MCH-R to be expressed in diverse brain areas implicated in the regulat ion of feeding, body adiposity, and sensory integration of smell and gustat ory inputs, including the hypothalamus [paraventricular nucleus (magnocellu lar 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 increas ed 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 R NA expression remains unaltered in genetic MCH deficiency. Our findings sug gest that MCH-R constitutes a central target of leptin action in the mammal ian brain.