Dataset Information

Effect of polyunsaturated fatty acids on postnatal ileum development using the fat-1 transgenic mouse model.

ABSTRACT:

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.

SUBMITTER: Singh P

PROVIDER: S-EPMC6397682 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Effect of polyunsaturated fatty acids on postnatal ileum development using the fat-1 transgenic mouse model.

Singh Pratibha P Ochoa-Allemant Pedro P Brown Joanne J Perides George G Freedman Steven D SD Martin Camilia R CR

Pediatric research 20190117 4

<h4>Background</h4>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.<h4>Methods</h4>Distal ileum sections were collected from fat-1 and WT mice on days 3, 14, and 28. Fatty acid analyses, histol ...[more]

PMID: 30653193

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Project description:Alcohol-associated liver disease (ALD) is the leading cause of liver disease worldwide, and alcohol-associated hepatitis (AH), a severe form of ALD, is a major contributor to the mortality and morbidity due to ALD. Many factors modulate susceptibility to ALD development and progression, including nutritional factors such as dietary fatty acids. Recent work from our group and others showed that modulation of dietary or endogenous levels of n6-and n3-polyunsaturated fatty acids (PUFAs) can exacerbate or attenuate experimental ALD, respectively. In the current study, we interrogated the effects of endogenous n3-PUFA enrichment in a mouse model which recapitulates features of early human AH using transgenic fat-1 mice which endogenously convert n6-PUFAs to n3-PUFAs. Male wild type (WT) and fat-1 littermates were provided an ethanol (EtOH, 5% v/v)-containing liquid diet for 10 days, then administered a binge of EtOH (5 g/kg) by oral gavage on the 11th day, 9 h prior to sacrifice. In WT mice, EtOH treatment resulted in liver injury as determined by significantly elevated plasma ALT levels, whereas in fat-1 mice, EtOH caused no increase in this biomarker. Compared to their pair-fed controls, a significant EtOH-mediated increase in liver neutrophil infiltration was observed also in WT, but not fat-1 mice. The hepatic expression of several cytokines and chemokines, including Pai-1, was significantly lower in fat-1 vs WT EtOH-challenged mice. Cultured bone marrow-derived macrophages isolated from fat-1 mice expressed less Pai-1 and Cxcl2 (a canonical neutrophil chemoattractant) mRNA compared to WT when stimulated with lipopolysaccharide. Further, we observed decreased pro-inflammatory M1 liver tissue-resident macrophages (Kupffer cells, KCs), as well as increased liver T regulatory cells in fat-1 vs WT EtOH-fed mice. Taken together, our data demonstrated protective effects of endogenous n3-PUFA enrichment on liver injury caused by an acute-on-chronic EtOH exposure, a paradigm which recapitulates human AH, suggesting that n3-PUFAs may be a viable nutritional adjuvant therapy for this disease.

Dataset Information

Effect of polyunsaturated fatty acids on postnatal ileum development using the fat-1 transgenic mouse model.

Background

Methods

Results

Conclusions

Publications

Effect of polyunsaturated fatty acids on postnatal ileum development using the fat-1 transgenic mouse model.

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