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Submitted on April 10, 2003
Accepted on June 26, 2003
1 Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9 Canada.
* To whom correspondence should be addressed. E-mail: cerdarev{at}iats.csic.es.
Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin. In mammals, central AGRP expression is restricted to the arcuate nucleus where it plays a key role in the control of energy balance by antagonizing melanocortin effects at melanocortin 4 receptors (MC4R). In goldfish, MC4R is profusely expressed within the main brain areas for the control of energy balance, and central administration of agonist or antagonist analogs inhibits or stimulates food intake, respectively. Here, we demonstrate that the goldfish genome has a homologous gene to mammalian AGRP. Detailed brain mapping by in situ hybridization shows that AGRP is exclusively expressed in the ventrobasal hypothalamic lateral tuberal nucleus, the teleostean homolog of the arcuate nucleus. Fasting up regulates its mRNA levels in the lateral tuberal nucleus. In the periphery, AGRP is expressed in several tissues including ovary, muscle and ventral skin, suggesting that AGRP might regulate peripheral actions of melanocortin peptides. The results provide the first evidence for an endogenous melanocortin antagonist in non-tetrapod species, and suggest that hypothalamic overexpression during fasting might regulate the inhibitory effects of melanocortin peptides on food intake in goldfish.
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