Melanin-Concentrating Hormone as a Metabolic and Cognitive Regulatory Factor

Abstract

Melanin-concentrating hormone (MCH) is an orexigenic cyclic 19 amino acid neuropeptide, and the cell bodies of MCH-containing neurons are mainly present in the lateral hypothalamus and zona incerta that are recognized as the feeding center of mammalian brain. MCH receptors, MCH-1R and MCH-2R are also widely distributed in the brain areas, especially in the hippocampus, amygdala and cerebral cortex. These findings suggest that MCH may modulate the energy homeostasis and other activities of central nervous system. Central administration of MCH increases food intake and decreases energy expenditure. Diet-induced and genetically obese animals have increase in MCH tone in the brain which is suppressed by leptin treatment. Moreover, MCH-transgenic mice exhibit obese syndromes when fed on high-fat diet. On the other hand, the MCH- or MCH-1R-deficient mice showed the resistance to obesity induced high-fat diet. Furthermore, MCH produces anxiety and increases the hippocampal synaptic efficacy, resulting in the enhancement of learning and memory processes. Non-peptide antagonists for MCH-1R prevented the high-fat diet-induced obesity, and possess anxiety and antidepressant effect. These finding indicate the involvement of MCH in the development of obesity, memory and emotion. MCH receptor antagonist might be useful for the treatment of obese syndrom including psychological disorder related obesity.