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Published on: October 27, 2020
CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells
T G Moreira1,2,3,4, L S Horta5, A C Gomes-Santos5
1Departamento de Alimentos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil. tmoreira@bwh.harvard.edu.
Abstract:
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.
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