A Potential Role for the Secretogranin II-Derived Peptide EM66 in the Hypothalamic Regulation of Feeding Behavior

Abstract

EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells as well as in hypothalamic neurons. Although EM66 is abundant in the hypothalamus, its physiological function remains to be elucidated. The aim of the present study was to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behavior. We show that ICV administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 h, which is associated with an increase of hypothalamic POMC and MC3R mRNA levels and c-Fos immunoreactivity in the POMC neurons of the arcuate nucleus. By contrast, ICV injection of EM66 does not alter the hypothalamic expression of NPY and neither that of its Y1 and Y5 receptors. A 3-month high fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48-h fasting in HFD mice decreases the expression of POMC and SgII mRNA that is not observed in mice fed a standard chow. Together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide that regulates hypothalamic feeding behavior, at least in part, by activating the POMC neurons of the arcuate nucleus.

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