Conjugated Linoleic Acid Ameliorates Inflammation-Induced Colorectal Cancer in Mice through Activation of PPARγ

Abstract

Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPARgamma in immune and epithelial cells and PPARgamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPARgamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPARgamma-expressing floxed mice but not in the tissue-specific PPARgamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPARgamma-expressing, but not in the tissue-specific, PPARgamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPARgamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPARgamma-dependent mechanism.

Pigment Epithelium-derived Factor (PEDF) Promotes Tumor Cell Death by Inducing Macrophage Membrane Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)

“…3) ChIP and DNA pulldown assays showed that a PPRE spanning nucleotides Ϫ382 to Ϫ370 in the proximal region of the human TRAIL promoter bound to PPAR␥. Recent animal studies using PPAR␥-deficient mice have proposed that PPAR␥ acts as a tumor suppressor gene to prevent carcinogenesis in the liver (45) and colon (46). Because TRAIL is expressed in the immune system and exerts a critical role in antitumor immunity (47), our study expanded the potential role of PPAR␥ and PEDF in tumor immunosurveillance mediated via macrophages.…”

Trans-10,cis-12-conjugated linoleic acid modulates NF-κB activation and TNF-α production in porcine peripheral blood mononuclear cells via a PPARγ-dependent pathway

“…Dietary CLA supplementation (mixture of isomers 9, 11 and 10, 12) up-regulated colonic PPARg expression and contributed to delaying the onset of experimental inflammatory bowel disease in a pig model (43) . It has also been demonstrated that CLA ameliorates dextran sodium sulphate-induced colitis (44) and prevents colorectal tumour formation, partly through a PPARg-dependent mechanism in PPARg-null mice (45) . c9t11-CLA reduced allergic sensitisation and airway inflammation in mice, most probably via a PPARg-related mechanism and by reducing eicosanoid precursors (46) .…”

Effects of dietary conjugated linoleic acid on the duodenal mucosal immunity response and redox status of broiler chicks infected with Eimeria aceruvlina

“…interferon γ (INFγ) and interleukin-10 (IL-10)) and T lymphocyte subset distributions . Dietary CLA reduced the proportion of macrophages in the mouse mesenteric lymph, inhibited the expression of colonic TNFα, and prevented the colon cancer development induced by inflammation (Evans et al 2010). Moreover, some studies have revealed the antioxidant properties of CLA (van Den Berg et al 1995;Yu 2001).…”