Article Text

PDF
OC-106 Activation of the bile acid receptor, farnesoid-x receptor, may reduce ileal inflammatory cytokine expression in an animal model of diet-induced obesity
  1. RA Speight1,2,
  2. A Whitehead3,
  3. G Patman3,
  4. JC Mansfield2,
  5. H Reeves3,
  6. JA Kirby1
  1. 1ICM, Newcastle University
  2. 2Gastroenterology, Newcastle U Tyne NHS Foundation Trust
  3. 3NICR, Newcastle University, Newcastle U Tyne, UK

Abstract

Introduction A high fat (HF)/high sugar (HS), Western diet has been implicated in the pathogenesis of IBD.1The BA receptor, farnesoid-x receptor (FXR), is central to the crosstalk between the host and its microbiota.2FXR has an immuno-modulatory role in the GI tract.3,4We hypothesised that disruption to BA signalling, induced by a HF/HS diet associated dysbiosis, is a mechanism linking diet to the development of IBD. The aim of this study was to investigate the effect of HF/HS feeding and FXR agonism on ileal inflammation in a mouse model of obesity.

Method Animal husbandry was performed under licence from the Home Office (as per ASPA 1986). C3H/He mice (n = 44) were fed standard chow or HF/HS chow (trans-fats, with fructose corn syrup). At 24 weeks, feed was supplemented with an FXR agonist (5 mg/kg or 1 mg/kg of feed) or control. At 42 weeks, body weight and visceral adipose tissue (VAT) weight was recorded and the ileum was dissected. The expression of TNFα, IFNγ and IL-6 was measured by RT-PCR (ΔΔCt method). FXR and its downstream targets, SHP and IBABP, were measured to assay for FXR activity. T-tests, regression analysis and Pearson correlation were calculated using Prism version 6.0e. P values were 2-tailed, a P value of <0.05 was considered significant.

Results Mice fed a HF/HS diet were significantly heavier, with more VAT than mice on the control diet (mean weight of 49.9 g versus mean weight of 41.6 g, p < 0.01). There was a positive correlation between the amount of VAT and the ileal expression of TNFα and IFNγ (y = 1.32*X p = 0.05, y = 1.24*X p = 0.02 respectively). The FXR agonist significantly increased the expression of IBABP (fold increase of 2.0, p = 0.01). In HF/HS fed mice, supplementation with 1 mg/kg FXR agonist attenuated the increase in ileal expression of all cytokines assayed, although the observed trend failed to reach significance.

Conclusion Animals fed a western lifestyle diet express more ileal inflammatory cytokine. There is a trend to suggest that supplementation with an FXR agonist reduces diet induced cytokine expression. By mediating dietary risk, FXR may be a potential therapeutic target in IBD, particularly to reduce relapses in patients with known disease.

Disclosure of interest None Declared.

References

  1. Ananthakrishnan AN. Gastroenterol Hepatol. 2013;9(6)

  2. Swann JR, Want EJ, et al. PNAS 2011;108(1)

  3. Vavassori P, Mencarelli A, et al. J Immunol. 2009;183

  4. Gadaleta RM, van Erpecum KJ, et al. Gut 2011;60

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.