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.
Highlights
The prevalence of obesity has been increasing substantially in the developed countries reaching epidemic proportions [1,2]
The increased risk of colorectal cancer (CRC) linked to obesity might rely on the local aberrant activation of inflammatory pathways establishing a chronic low-grade inflammatory condition, which may predispose to cancer development
To evaluate whether obesity and/or CRC influence the expression/activation of transcription factors critically involved in the regulation of inflammation, the expression of phosphorylated form of STAT3 (pSTAT3) and of nuclear peroxisome proliferatoractivated receptor γ (PPARγ) were assessed in visceral adipocytes isolated from the four groups of subjects
Summary
The prevalence of obesity has been increasing substantially in the developed countries reaching epidemic proportions [1,2]. This poses a great challenge to global health as obesity represents a main risk factor for a number of chronic degenerative diseases. The role of body fatness as a risk factor for CRC has been documented; in particular, it has been recently demonstrated that obesity shows a stronger positive correlation with the risk of developing colon cancer rather than rectal cancer [7,8,9]. A critical barrier to progress into the field is represented by the still poor knowledge on how adipose tissue metabolism can impact cancer development
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