Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

Abstract

A central event in inflammatory bowel disease is the disruption of the mucosal homeostasis. Trefoil peptides [(TFF)] are emerging as key mediators in the defense and repair of the gastrointestinal mucosa. Here, we demonstrate induction of TFF by CLA with therapeutic antiinflammatory effects in a mouse model of inflammatory bowel disease. SW480 cells were treated with linoleic acid or CLA (0-2.5 μmol/L) in the absence or presence of the PPARγ inhibitor GW9662. Cells treated with CLA showed an upregulation of the intestinal trefoil factor, which was prevented by pretreatment with GW9662. Dextran sulfate sodium (2%) was used to induce colitis in mice and they were simultaneously fed with a standard or a CLA-supplemented (100 mg · kg(-1) · d(-1)) diet for 7 d. The CLA-enriched diet prevented the colon shortening induced by DSS and markedly reduced the disease activity index and the colonic expression of inducible NO synthase and NF-κB. Immunohistochemistry revealed an increase in PPARγ and TFF3 expression after CLA administration. Altogether, these results indicate that dietary CLA protects against DSS-induced colitis in a process involving induction of PPARγ and TFF3.

Dietary n-3 polyunsaturated fatty acids ameliorate Crohn's disease in rats by modulating the expression of PPAR-γ/NFAT

“…The results of the current study revealed that n-3 PUFA intake activated PPAR-γ expression in healthy rats and TNBS-induced CD rats. Therefore, the protective effects of n-3 PUFA may be attributed to the activation and increased expression of PPAR-γ, which was consistent with a previous study (30). PPAR-γ usually exists as a heterodimer with retinoid X receptor, and has been reported to be associated with PPAR response elements in the regulation of NFAT, a transcription factor that binds to the IL-2 and IL-4 promoters and is necessary for gene transcription (18,38).…”

“…Previous studies have demonstrated the association between dietary fat and IBD. Borniquel et al (30) reported that dietary conjugated linoleic acid ameliorated colonic inflammation induced by dextran sulfate sodium in mice. In addition, another study demonstrated the efficacy of short chain fatty acids in accelerating clinical disease in an IL-10 -/mouse model (31).…”

Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease

“…Immunohistochemical staining of frozen colon sections was performed as previously described [38] to asses levels of inducible NO synthase (iNOS), NFκB p65 (Santa Cruz Biotechnology, CA, USA) and mucin 2 (Muc2) (Abcam, Cambridge, UK). Secondary antibodies were biotinylated anti-mouse and anti-rabbit IgG (Jackson Immunoresearch Laboratories, PA, USA).…”

Conjugated Linoleic Acid Effects on Cancer, Obesity, and Atherosclerosis: A Review of Pre-Clinical and Human Trials with Current Perspectives

“…The reason for this loss of adiponectin is unclear, but a recent study by our group suggests that by at least partially restoring the adiponectin levels, co-treatment with the thiazolidinedione rosiglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist that directly upregulates adiponectin [101], also improves glucose metabolism, while still allowing for CLA-mediated weight loss [102]. While some studies suggest that CLA is a PPARγ agonist [103,104,105,106,107], the majority of studies to date have shown that CLA decreases PPARγ mRNA expression, activation, and downstream targets [100,108,109,110,111,112]. Thus, we are beginning to understand that CLA promotes a form of weight loss that is not especially metabolically healthy, as evidenced by the reduced PPARγ activity and adiponectin levels.…”