The melanocortin MC(3) receptor remains the most enigmatic of the melanocortin receptors with regard to its physiological functions. The receptor is expressed both in the CNS and in multiple tissues in the periphery. It appears to be an inhibitory autoreceptor on proopiomelanocortin neurons, yet global deletion of the receptor causes an obesity syndrome. Knockout of the receptor increases adipose mass without a readily measurable increase in food intake or decrease in energy expenditure. And finally, no melanocortin MC(3) receptor null humans have been identified and associations between variant alleles of the melanocortin MC(3) receptor and diseases remain controversial, so the physiological role of the receptor in humans remains to be determined.
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