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

Abstract

ObjectiveThe 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).MethodsHuman 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.ResultsWe 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.ConclusionOur 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.

Very-long-chain ω-3 fatty acid supplements and adipose tissue functions: a randomized controlled trial

“…For practical reasons we did not measure inflammatory responses in visceral fat, a depot known to be inherently more immune-cell infiltrated than subcutaneous fat. Some investigators have reported positive effects of v-3 fatty acid supplements on visceral fat (46,47), and others have noted that greater self-reported v-3 fatty acid intakes are negatively associated with visceral fat and percentage of body fat in healthy children (48). We cannot know whether there might have been a beneficial effect of v-3 fatty acids on visceral fat inflammation in our participants, but if there was it did not improve inflammatory markers (26) or insulin sensitivity.…”

Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology

“…However, DHA does not directly bind to this class of transcription factor. With respect to colon cancer, DHA exhibits a protective suppressive effect against hyperactivated STAT3 and may reestablish the equilibrium between STAT3 and PPARγ (42). The decrease in STAT3 activity may be associated with the ability of n-3 PUFA to trigger PPARγ-RXR heterodimers to localize at their cognate PPAR response elements and exchange corepressors for coactivators such as CREB binding protein and p300 (52).…”

ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies

“…In this regard, it is of relevance that ω3/ω6 PUFA ratio of the industrialized diets is imbalanced, and this condition results in a well-known pro-inflammatory effect (22). Noteworthy, a decreased ω3/ω6 PUFA ratio of visceral AT correlates with AT inflammatory status in CRC patients suggesting that qualitative, more than quantitative, PUFA changes in AT may influence tissue dysfunctions potentially linked to inflammatory conditions (23). Likewise, the sum of some PUFA [i.e., gamma linolenic acid (GLA), Di-homo-gamma linolenic acid (DGLA), and arachidonic acid (AA)] in both visceral and subcutaneous AT was found statistically higher in cancer patients with respect to healthy controls (24).…”