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.