Effect of polyunsaturated fatty acids on postnatal ileum development using the fat-1 transgenic mouse model
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Updated: Jan 30, 2026
Dietary Supplementation of Polyunsaturated Fatty Acids in Caenorhabditis elegans
Published on: November 29, 2013
Pratibha Singh1, Pedro Ochoa-Allemant1, Joanne Brown1
1Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Insights
Long-chain polyunsaturated fatty acids (LCPUFAs) are crucial for infant gut development. Early LCPUFA profiles influence intestinal gene expression related to cell differentiation and immune response.
Area of Science:
- Neonatal nutrition
- Gastrointestinal development
- Fatty acid metabolism
Background:
- Long-chain polyunsaturated fatty acids (LCPUFAs) are vital for neonatal health.
- LCPUFAs are hypothesized to prime postnatal gut development.
- Studies utilize fat-1 transgenic mice for altered LCPUFA synthesis.
Purpose of the Study:
- To investigate the role of LCPUFAs in postnatal gut development.
- To examine the impact of altered LCPUFA profiles on intestinal gene expression.
- To assess changes in innate immunity and cell differentiation markers.
Main Methods:
- Ileum tissue collected from fat-1 and wild-type (WT) mice at postnatal days 3, 14, and 28.
- Analysis included fatty acid profiling, histology, RT-qPCR, and intestinal permeability assays.
- Gene expression of innate immune markers, cell differentiation, and lipid metabolism regulators were quantified.
Main Results:
- Fat-1 mice exhibited higher n-3 LCPUFA levels and lower arachidonic acid in the ileum.
- Preweaning fat-1 mice showed reduced expression of innate immune markers (muc2, Tff3, TLR9, Camp).
- Increased expression of cell differentiation (Fzd5, EphB2) and fatty acid transport (Fabp2, 6) genes observed in fat-1 mice.
Conclusions:
- Early LCPUFA profiles modulate intestinal gene expression.
- Key developmental domains affected include cell differentiation, innate host defenses, and lipid metabolism.
- Despite altered gene expression, intestinal permeability remained comparable between groups.
Background:
Long-chain polyunsaturated fatty acids (LCPUFAs) play a critical role in neonatal health. We hypothesized that LCPUFAs play an essential role in priming postnatal gut development. We studied the effect of LCPUFAs on postnatal gut development using fat-1 transgenic mice, which are capable of converting n-6 to n-3 LCPUFAs, and wild-type (WT) C57BL/6 mice.
Methods:
Distal ileum sections were collected from fat-1 and WT mice on days 3, 14, and 28. Fatty acid analyses, histology, RT-qPCR and intestinal permeability were performed.
Results:
Fat-1 mice, relative to WT mice, showed increased n-3 LCPUFAs levels (α-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid, p < 0.05) and decreased arachidonic acid levels (p < 0.05) in the ileum. Preweaning fat-1 mice, compared to WT, showed >50% reduced muc2, Tff3, TLR9, and Camp expression (p < 0.05), markers of the innate immune response. There was a >two-fold increased expression of Fzd5 and EphB2, markers of cell differentiation (p < 0.05), and Fabp2 and 6, regulators of fatty acid transport and metabolism (p < 0.05). Despite reduced expression of tight junction genes, intestinal permeability in fat-1 was comparable to WT mice.
Conclusions:
Our data support the hypothesis that fatty acid profiles early in development modulate intestinal gene expression in formative domains, such as cell differentiation, tight junctions, other innate host defenses, and lipid metabolism.
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