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Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ?6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells.


ABSTRACT: Obesity is a low-grade chronic inflammatory state representing an important risk factor for colorectal cancer (CRC). Adipocytes strongly contribute to inflammation by producing inflammatory mediators. In this study we investigated the role of human visceral fat adipocytes in regulating the functions of innate immunity cells. Adipocyte-conditioned media (ACM) from obese (n = 14) and CRC (lean, n = 14; obese, n = 13) subjects released higher levels of pro-inflammatory/immunoregulatory factors as compared to ACM from healthy lean subjects (n = 13). Dendritic cells (DC), differentiated in the presence of ACM from obese and CRC subjects, expressed elevated levels of the inhibitory molecules PD-L1 and PD-L2, and showed a reduced IL-12/IL-10 ratio in response to both TLR ligand- and ?? T lymphocyte-induced maturation. Furthermore, CRC patient-derived ACM inhibited DC-mediated ?? T cell activation. The immunosuppressive signals delivered by ACM from obese and CRC individuals were associated with a pro-inflammatory secretory and ?6 polyunsaturated fatty acid profile of adipocytes. Interestingly, STAT3 activation in adipocytes correlated with dihomo-?linolenic acid content and was further induced by arachidonic acid, which conversely down-modulated PPAR?. These results provide novel evidence for a cross-talk between human adipocytes and innate immunity cells whose alteration in obesity and CRC may lead to immune dysfunctions, thus setting the basis for cancer development.

SUBMITTER: Del Corno M 

PROVIDER: S-EPMC5325349 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ω6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells.

Del Cornò Manuela M   D'Archivio Massimo M   Conti Lucia L   Scazzocchio Beatrice B   Varì Rosaria R   Donninelli Gloria G   Varano Barbara B   Giammarioli Stefania S   De Meo Simone S   Silecchia Gianfranco G   Pennestrì Francesco F   Persiani Roberto R   Masella Roberta R   Gessani Sandra S  

Oncotarget 20160901 39


Obesity is a low-grade chronic inflammatory state representing an important risk factor for colorectal cancer (CRC). Adipocytes strongly contribute to inflammation by producing inflammatory mediators. In this study we investigated the role of human visceral fat adipocytes in regulating the functions of innate immunity cells. Adipocyte-conditioned media (ACM) from obese (n = 14) and CRC (lean, n = 14; obese, n = 13) subjects released higher levels of pro-inflammatory/immunoregulatory factors as c  ...[more]

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