Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity
The development of BPD in preterm neonates is increased by poor growth and nutritional deficits. The involvement of the fatty acid DHA in the development of BPD has been a focus for over a decade. However, recent clinical trials show that isolated DHA supplementation may increase BPD in subgroups of...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/4/551 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849712375778770944 |
|---|---|
| author | Adrienne J. Cohen Wesley R. Chidester Daniel T. Wray Nicolette Jessen Aimee Jones Cheylah Bitsui James Zhao J. Alan Maschek James E. Cox Camilia R. Martin Lisa A. Joss-Moore |
| author_facet | Adrienne J. Cohen Wesley R. Chidester Daniel T. Wray Nicolette Jessen Aimee Jones Cheylah Bitsui James Zhao J. Alan Maschek James E. Cox Camilia R. Martin Lisa A. Joss-Moore |
| author_sort | Adrienne J. Cohen |
| collection | DOAJ |
| description | The development of BPD in preterm neonates is increased by poor growth and nutritional deficits. The involvement of the fatty acid DHA in the development of BPD has been a focus for over a decade. However, recent clinical trials show that isolated DHA supplementation may increase BPD in subgroups of preterm neonates. One explanation for poor lung outcomes in DHA-supplemented neonates is a disruption of global fatty acid profiles and increased expression of a dominant-negative splice variant of a key driver of lung development, PPARγ. We previously developed a rat model of postnatal growth restriction (PGR) in which pups have impaired lung function and altered PPARγ activity. Here, we use our PGR rat model to assess the effects of DHA supplementation on lung outcomes. We hypothesize that the PPARγ splice variant, PPARγΔ5, will be expressed in the rat lung, and that DHA supplementation of PGR rat pups will alter circulating lipid profiles, lung mechanics, and PPARγ variant expression. Our findings demonstrate that PPARγΔ5 is expressed in the developing rat lung and that DHA supplementation of PGR rat pups alters global circulating fatty-acid profiles and does not normalize PGR-induced impaired lung mechanics or PPARγ activity. |
| format | Article |
| id | doaj-art-3bc5e3f29eaf49d39e46a6f5f0247b76 |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-3bc5e3f29eaf49d39e46a6f5f0247b762025-08-20T03:14:17ZengMDPI AGBiomolecules2218-273X2025-04-0115455110.3390/biom15040551Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ ActivityAdrienne J. Cohen0Wesley R. Chidester1Daniel T. Wray2Nicolette Jessen3Aimee Jones4Cheylah Bitsui5James Zhao6J. Alan Maschek7James E. Cox8Camilia R. Martin9Lisa A. Joss-Moore10Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USAHealth Science Center Cores, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USAHealth Science Center Cores, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USADivision of Neonatology, Weill Cornell Medicine, New York, NY 10065, USADepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USAThe development of BPD in preterm neonates is increased by poor growth and nutritional deficits. The involvement of the fatty acid DHA in the development of BPD has been a focus for over a decade. However, recent clinical trials show that isolated DHA supplementation may increase BPD in subgroups of preterm neonates. One explanation for poor lung outcomes in DHA-supplemented neonates is a disruption of global fatty acid profiles and increased expression of a dominant-negative splice variant of a key driver of lung development, PPARγ. We previously developed a rat model of postnatal growth restriction (PGR) in which pups have impaired lung function and altered PPARγ activity. Here, we use our PGR rat model to assess the effects of DHA supplementation on lung outcomes. We hypothesize that the PPARγ splice variant, PPARγΔ5, will be expressed in the rat lung, and that DHA supplementation of PGR rat pups will alter circulating lipid profiles, lung mechanics, and PPARγ variant expression. Our findings demonstrate that PPARγΔ5 is expressed in the developing rat lung and that DHA supplementation of PGR rat pups alters global circulating fatty-acid profiles and does not normalize PGR-induced impaired lung mechanics or PPARγ activity.https://www.mdpi.com/2218-273X/15/4/551lung developmentgrowth restrictionbronchopulmonary dysplasiaDHAPPARγalternative splicing |
| spellingShingle | Adrienne J. Cohen Wesley R. Chidester Daniel T. Wray Nicolette Jessen Aimee Jones Cheylah Bitsui James Zhao J. Alan Maschek James E. Cox Camilia R. Martin Lisa A. Joss-Moore Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity Biomolecules lung development growth restriction bronchopulmonary dysplasia DHA PPARγ alternative splicing |
| title | Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity |
| title_full | Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity |
| title_fullStr | Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity |
| title_full_unstemmed | Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity |
| title_short | Docosahexaenoic Acid Supplementation in Postnatal Growth Restricted Rats Does Not Normalize Lung Function or PPARγ Activity |
| title_sort | docosahexaenoic acid supplementation in postnatal growth restricted rats does not normalize lung function or pparγ activity |
| topic | lung development growth restriction bronchopulmonary dysplasia DHA PPARγ alternative splicing |
| url | https://www.mdpi.com/2218-273X/15/4/551 |
| work_keys_str_mv | AT adriennejcohen docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT wesleyrchidester docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT danieltwray docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT nicolettejessen docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT aimeejones docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT cheylahbitsui docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT jameszhao docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT jalanmaschek docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT jamesecox docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT camiliarmartin docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity AT lisaajossmoore docosahexaenoicacidsupplementationinpostnatalgrowthrestrictedratsdoesnotnormalizelungfunctionorppargactivity |