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Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ
Adrienne J Cohen1, Wesley R Chidester1, Daniel T Wray1
1Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USA.
Biomolecules
|April 30, 2025
Summary
Docosahexaenoic acid (DHA) supplementation may worsen bronchopulmonary dysplasia (BPD) in preterm infants by disrupting fatty acid profiles and altering PPARγ activity. This study found DHA did not improve lung function in a rat model of growth restriction.
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Nutritional science
Background:
- Bronchopulmonary dysplasia (BPD) is a common complication in preterm neonates, often linked to poor growth and nutritional deficits.
- Docosahexaenoic acid (DHA) supplementation has been investigated for BPD, but recent trials suggest potential harm in specific subgroups.
- Altered fatty acid profiles and aberrant expression of peroxisome proliferator-activated receptor gamma (PPARγ) are implicated in poor lung outcomes.
Purpose of the Study:
- To investigate the effects of DHA supplementation on lung outcomes in a rat model of postnatal growth restriction (PGR).
- To determine if DHA alters circulating lipid profiles, lung mechanics, and PPARγ variant expression in PGR rat pups.
- To assess the expression of the PPARγ splice variant, PPARγΔ5, in the developing rat lung.
Main Methods:
- Utilized a previously established rat model of postnatal growth restriction (PGR).
- Administered DHA supplementation to PGR rat pups.
- Assessed circulating lipid profiles, lung mechanics, and PPARγ variant expression (including PPARγΔ5).
Main Results:
- The PPARγ splice variant, PPARγΔ5, was confirmed to be expressed in the developing rat lung.
- DHA supplementation in PGR rat pups altered global circulating fatty-acid profiles.
- DHA supplementation did not normalize the impaired lung mechanics or altered PPARγ activity associated with PGR.
Conclusions:
- PPARγΔ5 is present in the developing rat lung and may play a role in lung development.
- DHA supplementation in the context of growth restriction does not improve lung function and alters systemic fatty acid metabolism.
- Further research is needed to understand the complex interactions between fatty acids, PPARγ, and lung development in preterm neonates.

