Role of melanocortinergic neurons in feeding and the agouti obesity syndrome View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-01

AUTHORS

W Fan, B A Boston, R A Kesterson, V J Hruby, R D Cone

ABSTRACT

Dominant alleles at the agouti locus (A) cause an obesity syndrome in the mouse, as a consequence of ectopic expression of the agouti peptide. This peptide, normally only found in the skin, is a high-affinity antagonist of the melanocyte-stimulating hormone receptor (MC1-R), thus explaining the inhibitory effect of agouti on eumelanin pigment synthesis. The agouti peptide is also an antagonist of the hypothalamic melanocortin-4 receptor (MC4-R). To test the hypothesis that agouti causes obesity by antagonism of hypothalamic melanocortin receptors, we identified cyclic melanocortin analogues that are potent agonists or antagonists of the neural MC3 (refs 11, 12) and MC4 receptors. Intracerebroventricular administration of the agonist, MTII, inhibited feeding in four models of hyperphagia: fasted C57BL/6J, ob/ob, and A(Y) mice, and mice injected with neuropeptide Y. Co-administration of the specific melanocortin antagonist and agouti-mimetic SHU9119 completely blocked this inhibition. Furthermore, administration of SHU9119 significantly enhanced nocturnal feeding, or feeding stimulated by a prior fast. Our data show that melanocortinergic neurons exert a tonic inhibition of feeding behaviour. Chronic disruption of this inhibitory signal is a likely explanation of the agouti obesity syndrome. More... »

PAGES

165-168

Journal

TITLE

Nature

ISSUE

6612

VOLUME

385

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/385165a0

    DOI

    http://dx.doi.org/10.1038/385165a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1028016940

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/8990120


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