Document Type
Article
Publication Date
2-2025
Publisher
Elsevier
Source Publication
Respiratory Physiology & Neurobiology
Source ISSN
1569-9048
Original Item ID
DOI: 10.1016/j.resp.2024.104370
Abstract
Obesity increases the risk of respiratory diseases that reduce respiratory chemosensitivity, such as Obesity Hypoventilation Syndrome and sleep apnea. Recent evidence suggests that obesity-related changes in the brain, including alterations in melanocortin signaling via the melanocortin-4 receptor (MC4R), may underly altered chemosensitivity. Setmelanotide, an MC4R agonist, causes weight loss in both humans and animal models. However, it is unknown the extent to which setmelanotide affects respiratory chemosensitivity independent of body weight loss. The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR). We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR. In a separate group of animals, we find that we can emulate setmelanotide’s effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide. These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide. We conclude that acute treatment with setmelanotide is as effective as weight loss at improving respiratory hypercapnic chemosensitivity.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Framnes-DeBoer, Sarah N.; Arble, Deanna M.; and Rivera, Athena, "The MC4R Agonist, Setmelanotide, Is Associated with an Improvement in Hypercapnic Chemosensitivity and Weight Loss in Male Mice" (2025). Biological Sciences Faculty Research and Publications. 969.
https://epublications.marquette.edu/bio_fac/969
Comments
Published version. Respiratory Physiology & Neurobiology, Vol. 332 (February-March 2025). DOI. © 2025 Elsevier. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).