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A potential role for the secretogranin II ‐derived peptide EM 66 in the hypothalamic regulation of feeding behaviour
Author(s) -
Trebak F.,
Dubuc I.,
Arabo A.,
Alaoui A.,
Boukhzar L.,
Maucotel J.,
Picot M.,
Cherifi S.,
Duparc C.,
Leprince J.,
Prévost G.,
Anouar Y.,
Magoul R.,
Chartrel N.
Publication year - 2017
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12459
Subject(s) - medicine , endocrinology , hypothalamus , neuropeptide y receptor , arcuate nucleus , receptor , neuropeptide , melanocortin , biology , messenger rna , proopiomelanocortin , chemistry , gene , biochemistry
EM 66 is a conserved 66‐amino acid peptide derived from secretogranin II (Sg II ), a member of the granin protein family. EM 66 is widely distributed in secretory granules of endocrine and neuroendocrine cells, as well as in hypothalamic neurones. Although EM 66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM 66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM 66 induces a drastic dose‐dependent inhibition of food intake in mice deprived of food for 18 hours, which is associated with an increase of hypothalamic pro‐opiomelanocortin (POMC) and melanocortin‐3 receptor mRNA levels and c‐Fos immunoreactivity in the POMC neurones of the arcuate nucleus. By contrast, i.c.v. injection of EM 66 does not alter the hypothalamic expression of neuropeptide Y ( NPY ), or that of its Y1 and Y5 receptors. A 3‐month high‐fat diet ( HFD ) leads to an important decrease of POMC and Sg II mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48 hours of fasting in HFD mice decreases the expression of POMC and Sg II mRNA , which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM 66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.