Liraglutide reduced lung inflammation and improved lung structure in newborn rats with hyperoxia-induced bronchopulmonary dysplasia by shifting the renin-angiotensin system toward its protective arm.
P < 0.05Significant reduction in harmful ACE/AngII/AT1R pathway activity and increase in protective ACE-2/Ang(1-7) levels at all three time points measured
What the researchers found
Liraglutide significantly reduced levels of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in bronchoalveolar lavage fluid and improved alveolar architecture in hyperoxia-exposed neonatal rats.
At the molecular level, liraglutide decreased mRNA and protein expression of ACE, AngII, and AT1R (P < 0.05) while increasing ACE-2 and Ang(1-7) expression (P < 0.05) at postnatal days 3, 7, and 14. When A779, a Mas receptor antagonist, was co-administered, liraglutide's protective effects were abolished, confirming the ACE-2/Ang(1-7)/Mas axis as the critical mechanism.
Why it matters
Bronchopulmonary dysplasia remains one of the most common and serious complications for premature infants, with limited treatment options. This study identifies a specific molecular mechanism through which a well-established GLP-1 drug could protect developing lungs, potentially opening a new therapeutic avenue for a vulnerable population.
How the study worked
Newborn Sprague-Dawley rats were divided into four groups: normal air control, hyperoxia-exposed (to induce BPD), hyperoxia plus liraglutide treatment, and hyperoxia plus liraglutide plus A779 (a blocker of the protective pathway). Lung tissues and fluid were collected at days 3, 7, and 14. Researchers used tissue staining to assess lung structure, ELISA to measure inflammatory markers, and RT-qPCR, Western blotting, and immunohistochemistry to measure molecular pathway activity.
What this study cannot tell us
This was an animal study using neonatal rats, so results may not directly translate to human premature infants. The study did not test different doses of liraglutide or examine long-term outcomes beyond 14 days. Additionally, the BPD model was induced purely by hyperoxia, which may not fully capture the multifactorial causes of BPD in clinical settings.
How to read the evidence
This is a preclinical animal study using a neonatal rat model. While it provides strong mechanistic evidence with multiple validated measurement methods and appropriate controls (including pathway blockade with A779), it has not been tested in humans.
When this study was published
Published in 2025, this is a very recent study reflecting current interest in repurposing GLP-1 drugs for non-metabolic conditions.
The bigger picture
GLP-1 receptor agonists like liraglutide are increasingly being studied for benefits beyond blood sugar control, including anti-inflammatory and organ-protective effects. This study adds neonatal lung protection to that expanding list and highlights the renin-angiotensin system as a key mediator, connecting GLP-1 biology to a pathway already of major interest in respiratory and cardiovascular medicine.
Questions still open
- Could liraglutide or other GLP-1 agonists be safe and effective for preventing BPD in premature human infants?
- What is the optimal dosing and timing window for liraglutide to maximize lung protection in neonatal models?
- Does this protective mechanism extend to other forms of neonatal lung injury beyond hyperoxia-induced damage?
Common questions
What is bronchopulmonary dysplasia and why is it a concern?
How does liraglutide protect the lungs in this study?
Read the original research
Bronchopulmonary dysplasia induced by hyperoxia attenuated by A GLP-1 analog, Liraglutide, by regulating the ACE-2/Ang(1-7)/Mas receptor pathway.
Pediatric research
Citation
Huang, Binglong; Luo, Han; Chen, Rou Yi; Li, Yeshan; Xiang, Min; Ao, Dang; Lin, Shaozhu; Liu, Ling. (2025). Bronchopulmonary dysplasia induced by hyperoxia attenuated by A GLP-1 analog, Liraglutide, by regulating the ACE-2/Ang(1-7)/Mas receptor pathway.. Pediatric research. https://doi.org/10.1038/s41390-025-04293-6