A potential role for the secretogranin II‐derived peptide EM66 in the hypothalamic regulation of feeding behaviour

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 neurones. Although EM66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM66 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 EM66 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 SgII 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 SgII mRNA, which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.

Characterization of the EM66 Biomarker in the Pituitary and Plasma of Healthy Subjects With Different Gonadotroph Status and Patients With Gonadotroph Tumor

“…EM66 has been identified in adult and fetal human adrenal gland (1) and subsequently in rat and bovine adrenochromaffin cells (2, 3). In rodents, EM66 immunoreactivity was also found in several hypothalamic regions (4, 5), which suggests several neuroendocrine roles for EM66 as it was proposed recently for the control of feeding behavior (6, 7). Moreover, we have previously demonstrated that measurement of tissue concentrations of EM66 may help to discriminate between benign and malignant pheochromocytomas (8–10) and that EM66 is secreted from pheochromocytoma tissue (11) and represents a sensitive plasma marker that should be considered as a complementary tool for the diagnosis and follow-up of pheochromocytoma (12–14).…”

Polysaccharides From Abrus cantoniensis Hance Modulate Intestinal Microflora and Improve Intestinal Mucosal Barrier and Liver Oxidative Damage Induced by Heat Stress

“…The hypothalamus is one of the important parts of the central nervous system, which has many functions such as balancing feeding, body temperature, and regulating endocrine. It can activate an emergency response to stressors in the environment ( 13 ). The hypothalamus-pituitary-adrenal (HPA) axis plays an important role in stimulating and integrating various physiological and neural responses to adverse stimuli ( 14 ).…”

“…Corticosterone (COR) is a glucocorticoid secreted by the adrenal cortex and has important implications for the HPA axis. COR is a sensitive index of HS response and is related to the metabolic rate and the caloric production of broilers ( 13 ). The increase in COR indicates that the HPA system is activated in response to HS ( 14 ).…”

A systematic review of chromogranin A (CgA) and its biomedical applications, unveiling its structure-related functions

“…CgB (formerly known as secretogranin I [15]) regulates the release of parathyroid hormones and is localized at chromaffin granule along with CgA [4]. CgC (formerly known as secretogranin II [15]) is also found in the nervous system [16] and is hypothesized to be a potential linker between the nervous and the immune systems [17]. Because human CgA is a crucial biomedical marker with a variety of functions in vivo, we will focus on human CgA in this review.…”