Des-acyl ghrelin and ghrelin O-acyltransferase regulate hypothalamic-pituitary-adrenal axis activation and anxiety in response to acute stress

Romana Stark, Vanessa V. Santos, Bram Geenen, Agustina Cabral, Tara Dinan, Jacqueline A. Bayliss, Sarah H. Lockie, Alex Reichenbach, Moyra B. Lemus, Mario Perello, Sarah J. Spencer, Tamas Kozicz, Zane B. Andrews

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Ghrelin exists in two forms in circulation, acyl ghrelin and des-acyl ghrelin, both of which have distinct and fundamental roles in a variety of physiological functions. Despite this fact, a large proportion of papers simply measure and refer to plasma ghrelin without specifying the acylation status. It is therefore critical to assess and state the acylation status of plasma ghrelin in all studies. In this study we tested the effect of des-acyl ghrelin administration onthe hypothalamic-pituitaryadrenal axis and on anxiety-like behavior of mice lacking endogenous ghrelin and in ghrelin-O-acyltransferase (GOAT) knockout (KO) mice that have no endogenous acyl ghrelin and high endogenous des-acyl ghrelin. Our results show des-acyl ghrelin produces an anxiogenic effect under nonstressed conditions, but this switches to an anxiolytic effect under stress. Des-acyl ghrelin influences plasma corticosterone under both nonstressed and stressed conditions, although c-fos activation in the paraventricular nucleus of the hypothalamus is not different. By contrast, GOAT KO are anxious under both nonstressed and stressed conditions, although this is not due to corticosterone release from the adrenals but rather from impaired feedback actions in the paraventricular nucleus of the hypothalamus, as assessed by c-fos activation. These results reveal des-acyl ghrelin treatment and GOAT deletion have differential effects on the hypothalamic-pituitaryadrenal axis and anxiety-like behavior, suggesting that anxiety-like behavior in GOAT KO mice is not due to high plasma des-acyl ghrelin.

Original languageEnglish (US)
Pages (from-to)3946-3957
Number of pages12
JournalEndocrinology
Volume157
Issue number10
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Des-acyl ghrelin and ghrelin O-acyltransferase regulate hypothalamic-pituitary-adrenal axis activation and anxiety in response to acute stress'. Together they form a unique fingerprint.

Cite this