Attenuation of colonic inflammation by partial replacement of dietary linoleic acid with α-linolenic acid in a rat model of inflammatory bowel disease

January 1, 2012 Human Health and Nutrition Data 0 Comments

Attenuation of colonic inflammation by partial replacement of dietary linoleic acid with α-linolenic acid in a rat model of inflammatory bowel disease

Year: 2012
Authors: Tyagi, A. Kumar, U. Reddy, S. Santosh, V.S. Mohammed, S.B. Ehtesham, N.Z. Ibrahim, A.
Publication Name: British Journal of Nutrition
Publication Details: doi:10.1017/S0007114511007197


Increasing prevalence of inflammatory bowel disease may be due to imbalance in the intake of n6 and n3 PUFA in the diet. This study investigates the impact of varying ratios of dietary linoleic acid (LA, 18:n6) to alpha linolenic acid (ALA, 18:n3) on the inflammatory response in dextran sulphate sodium (DSS) induced colitis. Weanling male Sprague Dawley rats were divided into five groups: a non-colitic group with a LA:ALA ratio of 215 (CON 215), and colitic groups with LA:ALA ratios of 215 (DSS 215), 50 (DSS 50), 10 (DSS 10) and 2 (DSS 2). Blends of groundnut, palmolein and linseed (flax) oils were used to provide varying LA:ALA ratios. All the rats were fed the respective experimental isoenergetic diets containing 10% fat for 90 d and DSS was administered during the last 11 d. Colonic inflammation was evaluated by clinical, biochemical and histological parameters. The results showed attenuation of colitis in the DSS 2 group as evidenced by significant reductions in disease activity index, mucosal myeloperoxidase activity (P<0.05), alkaline phosphatase activity (P<0.01) and increase in colon length (P<0.01) compared to the groups fed with higher ratios (DSS 215). This was accompanied by significant reductions in mucosal proinflammatory cytokines TNFa (P<0.01) and IL1b (P<0.01) and improvement in the histological score. Further, ALA supplementation increased long chain (LC) n3 PUFA and decreased LC n6 PUFA in colon structural lipids. These data suggest that substitution of one third of LA with ALA (LA:ALA ratio 2) mitigates experimental colitis by down-regulating proinflammatory mediators. (Authors abstract)
Ulcerative colitis (UC) and Crohn�s disease, the two types of inflammatory bowel disease (IBD), are characterised by recurrent episodes of inflammation and tissue degeneration. Beneficial effects of marine n3 PUFA in patients with IBD have been reported. The role of ALA has not been extensively investigated. The effects of increasing ALA and decreasing LA (varying the LA:ALA ratio) on inflammatory response in IBD have not been studied earlier. The present study investigates the effects of substituting dietary LA with ALA on colonic inflammation in the well established dextran sulphate sodium (DSS) induced model of UC by keeping total PUFA, MUFA and SFA constant.  The results demonstrated that rats which were fed a diet with a high LA:ALA ratio and subjected to DSS administration exhibit increased colonic inflammation. This was evidenced by increased DAI and histology scores, increased infiltration of inflammatory cells and production of proinflammatory cytokines in colonic mucosa. In contrast, the substitution of one-third of dietary LA with ALA (LA:ALA ratio of 2) resulted in significant protection from inflammatory damage. In addition, compared to the non colitic group, DSS treatment did not alter the colonic mucosal fatty acid composition (CON 215 vs. DSS 215). However, substituting varying levels of LA with ALA in DSS treated groups increased LC n3 PUFA and decreased the levels of LC n6 PUFA.  The observed reduction in inflammatory response by ALA supplementation could possibly be due to a marked reduction in arachidonic acid and an increase in EPA and DHA levels in the colon. n3 PUFA inhibit the production of pro inflammatory eicosanoids and the eicosanoids formed from EPA are less inflammatory. In addition, both ALA and LC n3 PUFA have been shown to down-regulate the expression of pro inflammatory genes through the inhibition of transcription factor NF kB.  In the present study, TNFa and IL1b levels in the colon of DSS administered rats which were fed a diet with a high LA:ALA ratio were significantly increased, suggesting that immune cells are attached to the site of inflammation. Substitution of LA with ALA suppressed inflammation by decreasing the production of pro inflammatory cytokines. The results suggest that ALA supplementation not only decreases pro inflammatory cytokine levels and reduces nitrosative stress, thereby offering protection against DSS induced colitis. In conclusion, the results of the present study demonstrate that varying LA:ALA ratios, representing a wide range of LA:ALA intake in the present human diet, modulate colonic inflammation in the DSS induced model of colitis. The LA:ALA ratio of 2 was optimal for protection against colitis as evidenced by the reduction in neutrophil infiltration, preservation of colonic architecture and reversal of the shortening of colon length as well as improvements in the symptoms of colitis. These effects were associated with decreased production of pro inflammatory mediators involved in the inflammatory response of the colon including cytokines such as TNFa, IL1b and NO. The authors suggest that the beneficial effects of ALA supplementation could be ascribed to the increased levels of LC n3 PUFA and decreased levels of LC n6 PUFA in the structural lipids of the colon. The results of this study hence reinforce the current recommendations for increasing n3 PUFA in the diet for the prevention of diet related chronic diseases. (Editors comments)

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