Poster Topical Area: Maternal, Perinatal and Pediatric Nutrition

Location: Hall D

Poster Board Number: 378

P13-121 - Effect of Fatty Acids on Postnatal Gut Development in Wild Type vs Fat-1 Transgenic Mice

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives
We hypothesized that long chain polyunsaturated fatty acids (LCPUFAs) play an important role in postnatal gut development. To test this hypothesis, we examined markers of gut development in Fat-1 transgenic vs wild type C57BL/6 mice on postnatal days 3, 14, and 28.
Methods
Wild-type (WT) and Fat-1 C57BL/6 transgenic mice were fed the same diet high in ω-6 LCPUFAs (AIN-76A with 10% corn oil), which in Fat-1 mice leads to an enrichment of ω-3 fatty acids from ω-6 precursors. Distal ileum sections were collected from Fat-1 and WT mice on days 3, 14, and 28. qRT-PCR, histology, and FAs analyses were performed. Fold changes in gene expression were quantified in Fat-1 mice relative to WT on each postnatal day and were considered significant if a > 2-fold reduced or increased change was noted with a p-value < .05.
Results
In Fat-1 compared to WT mice, ileum docosahexaenoic acid levels (mol%) increased by 2-fold on days 14 and 28. Similarly, eicosapentaenoic acid increased by 28-fold on days 3 and 14, and by 43-fold on day 28 (p<.05). There was a reciprocal 2-fold decrease in arachidonic acid (ω-6 fatty acid) on day 3 and 28 (p<.05). The ω3/ω6 ratio was significantly higher in Fat-1 compared to WT mice for all ages (p<.05). Histologic analyses showed reduced number of goblet cells in Fat-1 compared to WT mice on days 3 and 28 (p<.0001). Moreover, Fat-1 mice relative to WT showed a >2-fold reduction in the expression of innate immunity markers TLR9 (day 3; p=.003) and CAMP (days 3, 14, and 28; p=.005); >2 fold increase in gene expression of Wnt receptor Fzd5 and EphB2, which is linked to paneth cell differentiation (day 3, p<.001); and a >2 fold increased expression of I-FABP and FABP6, important regulators of fatty acid transport, cell growth and cell differentiation (day3, p<.001).
Conclusions
The Fat-1 transgenic mouse model provides an important tool to study the effect of omega-3 FAs on gut development. This model allows for well-controlled studies, without the interference of potential confounding factors of diet. These data demonstrate that LCPUFAs act as a potential regulator for early gut development by modulating the expression of several gut development markers. Future experiments using Fat-1 transgenic mice in inflammatory states such as necrotizing enterocolitis may elucidate the role of LCPUFAs in disease risk and pathogenesis.




Funding Source: Charles H. and Judy Hood Family Infant Health Research Program
NIH R01 DK104346

CoAuthors: Xinting Yu – Beth Israel Deaconess Medical Center; Pedro Ochoa Allemant – Beth Israel Deaconess Medical Center; George Perides – Beth Israel Deaconess Medical Center; Joanne Brown – Beth Israel Deaconess Medical Center; Steven Freedman – Beth Israel Deaconess Medical Center; Camilia Martin – Beth Israel Deaconess Medical Center

Pratibha Singh

Post-Doctoral Research Fellow
Beth Israel Deaconess Medical Center
Boston, Massachusetts