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Growth hormone-releasing hormone antagonistic analog MIA-690 stimulates food intake in mice.

Abstract
In addition to its metabolic and endocrine effects, growth hormone-releasing hormone (GHRH) was found to modulate feeding behavior in mammals. However, the role of recently synthetized GHRH antagonist MIA-690 and MR-409, a GHRH agonist, on feeding regulation remains to be evaluated. We investigated the effects of chronic subcutaneous administration of MIA-690 and MR-409 on feeding behavior and energy metabolism, in mice. Compared to vehicle, MIA-690 increased food intake and body weight, while MR-409 had no effect. Both analogs did not modify locomotor activity, as well as subcutaneous, visceral and brown adipose tissue (BAT) mass. A significant increase of hypothalamic agouti-related peptide (AgRP) gene expression and norepinephrine (NE) levels, along with a reduction of serotonin (5-HT) levels were found after MIA-690 treatment. MIA-690 was also found able to decrease gene expression of leptin in visceral adipose tissue. By contrast, MR-409 had no effect on the investigated markers. Concluding, chronic peripheral administration of MIA-690 could play an orexigenic role, paralleled by an increase in body weight. The stimulation of feeding could be mediated, albeit partially, by elevation of AgRP gene expression and NE levels and decreased 5-HT levels in the hypothalamus, along with reduced leptin gene expression, in the visceral adipose tissue.
AuthorsLucia Recinella, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V Schally, Luigi Brunetti, Sheila Leone
JournalPeptides (Peptides) Vol. 142 Pg. 170582 (08 2021) ISSN: 1873-5169 [Electronic] United States
PMID34051291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2021 Elsevier Inc. All rights reserved.
Chemical References
  • N-Me-Tyr1,D-Ala2,Asn8,Arg29-NHCH3-JI-38
  • Sermorelin
  • Growth Hormone-Releasing Hormone
Topics
  • Animals
  • Body Weight
  • Eating
  • Energy Metabolism
  • Feeding Behavior (drug effects)
  • Female
  • Gene Expression Regulation
  • Growth Hormone-Releasing Hormone (antagonists & inhibitors)
  • Hypothalamus (drug effects)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sermorelin (analogs & derivatives, pharmacology)

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