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Postnatal Growth Restriction and Docosahexaenoic Acid Supplementation Increases Expression of a Dominant Negative PPAR𝛄 Splice Variant in Rat Lung

Semester: Summer 2023

Presentation description

Postnatally growth restricted (PGR) preterm infants develop the lung disease bronchopulmonary dysplasia (BPD). BPD is characterized by impaired lung development with worse outcomes in males. Docosahexaenoic acid (DHA) is critical for lung development. However, clinical trials supplementing preterm infants with DHA suggests DHA may have detrimental effects on lung outcomes. Lung development depends upon the transcription factor PPAR𝛄. Our group recently identified a novel splice variant of PPAR𝛄 (PPAR𝛄𝛥5) in rat lung. PPAR𝛄𝛥5 is a dominant negative, thus an increase in PPAR𝛄𝛥5:PPAR𝛄 ratio reduces expression of critical PPAR𝛄 target genes. However, whether PGR or DHA alters the expression of PPAR𝛄𝛥5 is unknown.

We hypothesize PGR and DHA will increase PPAR𝛄𝛥5:PPAR𝛄 ratio in male, but not female rat lung.
PGR was induced by litter-size, with 8 (control) or 16 (PGR) pups/litter, and pups raised to day 21. Control litters received regular diet, and PGR litters were randomized diets with DHA at 0%, 0.01%, or 0.1%. PPAR𝛄𝛥5:PPAR𝛄 mRNA levels were measured by real-time RT-PCR. Males and females were treated as separate groups and differences were assessed using one way-ANOVA and FLD post-hoc tests.

In male rats, our results showed that PGR increased the lung PPAR𝛄𝛥5:PPAR𝛄 ratio (119±9%*). And PGR with DHA, further increased PPAR𝛄𝛥5:PPAR𝛄 ratio in male rat lung (0.01%-132±20, 0.1%-128±12%*). In female rats, neither PGR nor DHA altered lung PPAR𝛄𝛥5:PPAR𝛄.*P<0.05. Given that increased PPAR𝛄𝛥5:PPAR𝛄 ratio reduces the expression of PPAR𝛄 target genes, we speculate that increased an PPAR𝛄𝛥5:PPAR𝛄 ratio may impair lung development in males in the context of PGR and DHA.

Presenter Name: Cheylah Bitsui
Presentation Format: Virtual
Presentation #59
College: Medicine
School / Department: Pediatrics
Research Mentor: Lisa Joss-Moore
Date | Time: Thursday, Aug 3rd | 10:30 AM