Omega-3 polyunsaturated fatty acids ameliorate the severity of ileitis in the senescence accelerated mice (SAM)P1/Yit mice model

Abstract

Clinical studies using omega-3 polyunsaturated fatty acids (omega3-PUFA) to Crohn's disease (CD) are conflicting. Beneficial effects of dietary omega3-PUFA intake in various experimental inflammatory bowel disease (IBD) models have been reported. However, animal models of large intestinal inflammation have been used in all previous studies, and the effect of omega3 fat in an animal model of small intestinal inflammation has not been reported. We hypothesized that the effects of omega3 fat are different between large and small intestine. The aim of this study was to determine whether the direct effect of omega3 fat is beneficial for small intestinal inflammation. Senescence accelerated mice (SAM)P1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. The numbers of F4/80-positive monocyte-macrophage cells as well as beta7-integrin-positive lymphocytes in the intestinal mucosa were increased significantly compared with those in the control mice (AKR-J mice). The area of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-positive vessels was also increased. The degree of expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and interferon (IFN)-gamma mRNA were increased significantly compared with those in the control mice. The feeding of two different kinds of omega3 fat (fish-oil-rich and perilla-oil-rich diets) for 16 weeks to SAMP1/Yit mice ameliorated inflammation of the terminal ileum significantly. In both the omega3-fat-rich diet groups, enhanced infiltration of F4/80-positive monocytes/macrophages in intestinal mucosa of SAMP1/Yit mice cells and the increased levels of MCP-1, IL-6 and IFN-gamma mRNA expression were ameliorated significantly compared with those in the control diet group. The results suggest that omega3 fat is beneficial for small intestinal inflammation by inhibition of monocyte recruitment to inflamed intestinal mucosa.

Fig. 2

Representative haematoxylin and eosin sections (a–d). (a) AKR-J group. (b) Senescence accelerated mice (SAM)P1/Yit mice fed control diet. (c) SAMP1/Yit mice fed fish-oil-rich diet. (d) SAMP1/Yit mice fed perilla-oil-rich diet. (e) Weight of the ileum in all groups. (f) Total thickness of the ileum in all groups. (g) Muscular thickness of the ileum in all groups. Data are expressed as mean ± standard error. **P < 0·01 versus AKR-J group; #P < 0·05 versus SAMP1/Yit mice fed control diet; ##P < 0·01 versus SAMP1/Yit mice fed control diet.

Fig. 1

Time-course change of body weight. Senescence accelerated mice (SAM)P1/Yit, SAMP1/Yit mice fed control diet; SAM+Fish: SAMP1/Yit mice fed fish-oil-rich diet; SAM+Perilla: SAMP1/Yit mice fed perilla-oil-rich diet. Data are expressed as mean ± standard error. #P < 0·05 versus SAMP1/Yit mice fed control diet; *P < 0·01 versus SAMP1/Yit mice fed control diet.

Fig. 3

Immunohistochemistry for F4/80 (a–d). (a) AKR-J group. (b) Senescence accelerated mice (SAM)P1/Yit mice fed control diet. (c) SAMP1/Yit mice fed fish-oil-rich diet. (d) SAMP1/Yit mice fed perilla-oil-rich diet. (e) Number of F4/80 positive cells in all groups. (f) Relative mRNA expression level of monocyte chemoattrantant protein-1 (MCP-1) in all groups. (g) Relative mRNA expression level of interleukin (IL)-6 in all groups. Data are expressed as mean ± standard error. *P < 0·05 versus AKR-J group; **P < 0·01 versus AKR-J group; #P < 0·05 versus SAMP1/Yit mice fed control diet. ##P < 0·01 versus SAMP1/Yit mice fed control diet.

Fig. 4

Immunohistochemistry for mucosal addressin cell adhesion molecule-1 (MAdCAM-1) (a–d) and β7-integrin (f–i). (a) AKR-J group. (b) Senescence accelerated mice (SAM)P1/Yit mice fed control diet. (c) SAMP1/Yit mice fed fish-oil-rich diet. (d) SAMP1/Yit mice fed perilla-oil-rich diet. (e) Area of MAdCAM-1-positive vessels in the all groups. (f) AKR-J group. (g) SAMP1/Yit mice fed control diet. (h) SAMP1/Yit mice fed fish-oil-rich diet. (i) SAMP1/Yit mice fed perilla-oil-rich diet. (j) Number of β7-integrin positive cells in all groups.

Fig. 5

Immunohistochemistry for CD4 (a–d). (a) AKR-J group. (b) Senescence accelerated mice (SAM)P1/Yit mice fed control diet. (c) SAMP1/Yit mice fed fish-oil-rich diet. (d) SAMP1/Yit mice fed perilla-oil-rich diet. (e) Number of CD4 positive cells in all groups. (f) Relative mRNA expression level of interferon (IFN)-γ in all groups. Data are expressed as mean ± standard error. *P < 0·05 versus AKR-J group; # P < 0·05 versus SAMP1/Yit mice fed control diet; ## P < 0·01 versus SAMP1/Yit mice fed control diet.