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Mucosal Immunol. 2019 Jan;12(1):188-199. doi: 10.1038/s41385-018-0090-8. Epub 2018 Oct 2.

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

Author information

1
Departamento de Alimentos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil. tmoreira@bwh.harvard.edu.
2
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. tmoreira@bwh.harvard.edu.
3
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. tmoreira@bwh.harvard.edu.
4
Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. tmoreira@bwh.harvard.edu.
5
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
6
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
7
Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
8
Department of Medicine, School of Medicine, Johns Hopkins All Children's Hospital, Johns Hopkins University, St. Petersburg, FL, 33701, USA.
9
Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
10
Diabetes and Obesity Research Center, Sanford Burnham Medical Research Institute, Lake Nona, Orlando, FL, USA.
11
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. anacaetanofaria@gmail.com.

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.

PMID:
30279515
DOI:
10.1038/s41385-018-0090-8

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