ω3-PUFAs Exert Anti-Inflammatory Activity in Visceral Adipocytes from Colorectal Cancer Patients

• Published in: PloS one Vol. 8; no. 10; p. e77432
• Main Authors: D’Archivio, Massimo, Scazzocchio, Beatrice, Giammarioli, Stefania, Fiani, Maria L., Varì, Rosaria, Santangelo, Carmela, Veneziani, Augusto, Iacovelli, Annunziata, Giovannini, Claudio, Gessani, Sandra, Masella, Roberta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.10.2013; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipocytes - immunology; Adiponectin; Adiponectin - immunology; Adipose tissue; Aged; Anti-inflammatory agents; Anti-Inflammatory Agents - analysis; Anti-Inflammatory Agents - immunology; Antiinflammatory agents; Apoptosis; Body mass; Cancer; Cancer therapies; Cell growth; Cells, Cultured; Chromatography; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - complications; Colorectal Neoplasms - immunology; Correlation analysis; Cytokines; Docosahexaenoic acid; Equilibrium; Fatty acids; Fatty Acids, Omega-3 - analysis; Fatty Acids, Omega-3 - immunology; Female; Food safety; Hematology; Homeostasis; Humans; Immunoblotting; Inflammation; Interleukin-6 - immunology; Intra-Abdominal Fat - cytology; Male; Medical prognosis; Metabolism; Middle Aged; Obesity; Obesity - complications; Obesity - immunology; Patients; Polyunsaturated fatty acids; PPAR gamma - immunology; Public health; Stat3 protein; STAT3 Transcription Factor - immunology; Transcription factors; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077432

The aim of this study was to correlate specific fatty acid profiles of visceral white adipose tissue (WAT) with inflammatory signatures potentially associated with colorectal cancer (CRC). Human adipocytes were isolated from biopsies of visceral WAT from 24 subjects subdivided in four groups: normal-weight (BMI 22.0-24.9 Kg/m2) and over-weight/obese (BMI 26.0-40.0 Kg/m2), affected or not by CRC. To define whether obesity and/or CRC affect the inflammatory status of WAT, the activation of the pro-inflammatory STAT3 and the anti-inflammatory PPARγ transcription factors as well as the expression of adiponectin were analyzed by immunoblotting in adipocytes isolated from each group of subjects. Furthermore, to evaluate whether differences in inflammatory WAT environment correlate with specific fatty acid profiles, gas-chromatographic analysis was carried out on WAT collected from all subject categories. Finally, the effect of the ω3 docosahexaenoic acid treatment on the balance between pro- and anti-inflammatory factors in adipocytes was also evaluated. We provide the first evidence for the existence of a pro-inflammatory environment in WAT of CRC patients, as assessed by the up-regulation of STAT3, and the concomitant decrease of PPARγ and adiponectin with respect to healthy subjects. WAT inflammatory status was independent of obesity degree but correlated with a decreased ω3-/ω6-polyunsaturated fatty acid ratio. These observations suggested that qualitative changes, other than quantitative ones, in WAT fatty acid may influence tissue dysfunctions potentially linked to inflammatory conditions. This hypothesis was further supported by the finding that adipocyte treatment with docosahexaenoic acid restored the equilibrium between STAT3 and PPARγ. Our results suggest that adipocyte dysfunctions occur in CRC patients creating a pro-inflammatory environment that might influence cancer development. Furthermore, the protective potential of docosahexaenoic acid in re-establishing the equilibrium between pro- and anti-inflammatory factors might represent a useful tool for preventive and therapeutic strategies.