Hypothalamic injection of oxyntomodulin suppresses circulating ghrelin-like immunoreactivity.

Abstract:

:Ghrelin is a gastric peptide that regulates appetite and GH secretion. Circulating ghrelin levels are elevated by fasting and suppressed postprandially. However, the mechanisms regulating circulating ghrelin levels are unclear. Oxyntomodulin is an anorexic peptide hormone released from L cells in the gut. We investigated the effects of intracerebroventricular (icv) administration of oxyntomodulin on circulating ghrelin levels. The icv administration of 1, 3, or 10 nmol oxyntomodulin reduced circulating acylated and total (acylated and des-acylated) ghrelin 60 min after icv injection. Administration of 1 nmol oxyntomodulin directly into the arcuate nucleus of the hypothalamus significantly reduced total and acylated ghrelin levels, and administration of 3 nmol oxyntomodulin into the lateral ventricle induced c-fos mRNA expression in arcuate nucleus neurons expressing the glucagon-like peptide-1 (GLP-1) receptor. In a final study, the reduction in total ghrelin observed after icv injection of 3 nmol oxyntomodulin was blocked by coadministration of the GLP-1 receptor antagonist exendin (9-39). These studies suggest oxyntomodulin reduces peripheral ghrelin levels via GLP-1 receptor-dependent hypothalamic pathways. Postprandial release of anorexic gut hormones may thus act centrally to contribute to the postprandial reduction in circulating ghrelin.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Patterson M,Murphy KG,Patel SR,Patel NA,Greenwood HC,Cooke JH,Campbell D,Bewick GA,Ghatei MA,Bloom SR

doi

10.1210/en.2008-0796

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

3513-20

issue

8

eissn

0013-7227

issn

1945-7170

pii

en.2008-0796

journal_volume

150

pub_type

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