CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet...

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Bibliographic Details
Published in:Mucosal immunology 2019-01, Vol.12 (1), p.188-199
Main Authors: Moreira, T G, Horta, L S, Gomes-Santos, A C, Oliveira, R P, Queiroz, N M G P, Mangani, D, Daniel, B, Vieira, A T, Liu, S, Rodrigues, A M, Gomes, D A, Gabriely, G, Ferreira, E, Weiner, H L, Rezende, R M, Nagy, L, Faria, A M C
Format: Article
Language:English
Subjects:
Aminosalicylic Acid - metabolism
Animals
Anti-inflammatory agents
Azoxymethane
Carcinogenesis
Cell activation
Cells, Cultured
Colitis
Colitis - chemically induced
Colitis - immunology
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - chemically induced
Colorectal Neoplasms - immunology
Dextran
Dextran Sulfate
Diet
Dietary Supplements
Disease Models, Animal
Female
Humans
Inflammation
Inflammatory bowel disease
Inflammatory Bowel Diseases - immunology
Latency
Linoleic acid
Linoleic Acids, Conjugated - metabolism
Lymphocytes T
Macrophages
Macrophages - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mucosa
Peroxisome proliferator-activated receptors
PPAR gamma - genetics
PPAR gamma - metabolism
Sodium sulfate
T-Lymphocytes - immunology
Transforming Growth Factor beta - metabolism
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Summary:Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-β via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-β)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-018-0090-8