title: ω3-PUFAs exert anti-inflammatory activity in visceral adipocytes from colorectal cancer patients.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department Veterinary Public Health and Food Safety, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Archivio
authors.forename: Beatrice
authors.initials: B
authors.lastname: Scazzocchio
authors.forename: Stefania
authors.initials: S
authors.lastname: Giammarioli
authors.forename: Maria L
authors.initials: ML
authors.lastname: Fiani
authors.forename: Rosaria
authors.initials: R
authors.lastname: Varì
authors.forename: Carmela
authors.initials: C
authors.lastname: Santangelo
authors.forename: Augusto
authors.initials: A
authors.lastname: Veneziani
authors.forename: Annunziata
authors.initials: A
authors.lastname: Iacovelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Giovannini
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
authors.forename: Roberta
authors.initials: R
authors.lastname: Masella
mesh_terms: D017667:Adipocytes / Q000276:immunology*; D052242:Adiponectin / Q000276:immunology; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000276:immunology*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000150:complications / Q000276:immunology*; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000276:immunology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D050152:Intra-Abdominal Fat / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000276:immunology; D047495:PPAR gamma / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology
chemical_list: D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D015850:Interleukin-6; D047495:PPAR gamma; D050796:STAT3 Transcription Factor