Growth hormone-releasing hormone antagonistic analog MIA-690 stimulates food intake in mice.
Recinella. Lucia L; Chiavaroli. Annalisa A; Orlando. Giustino G; Ferrante. Claudio C; Gesmundo. Iacopo I; Granata. Riccarda R; Cai. Renzhi R; Sha. Wei W; Schally. Andrew V AV; Brunetti. Luigi L; Leone. Sheila S
Key Findings
- MIA‑690 (a GHRH antagonist) increased daily food intake and body weight in mice.
- MIA‑690 raised hypothalamic AgRP gene expression and norepinephrine levels while lowering serotonin, all signals that promote hunger.
- MIA‑690 reduced leptin gene expression in visceral fat, potentially reducing the satiety signal.
Practical Outcomes
- For self‑experimenters, the data suggest that blocking GHRH can stimulate appetite and weight gain, but the work is limited to mice and uses a compound not available for human use. It does not provide a usable protocol for people, but it highlights the GHRH pathway as a possible target for appetite manipulation and warns that GHRH antagonism may have unwanted weight‑gain effects.
Summary
In mice, a synthetic molecule that blocks growth‑hormone‑releasing hormone (called MIA‑690) made the animals eat more and gain weight. It did this by changing brain chemicals that control hunger and by lowering a fat‑signal hormone (leptin). The related GHRH‑activating molecule (MR‑409) did not change eating or weight.
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.
Study Information
pubmed
2021
2021-05-27T00:00:00.000Z
10.1016/j.peptides.2021.170582
5
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