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 γδ T lymphocyte-induced maturation. Furthermore, CRC patient-derived ACM inhibited DC-mediated γδ T cell activation. The immunosuppressive signals delivered by ACM from obese and CRC individuals were associated with a pro-inflammatory secretory and ω6 polyunsaturated fatty acid profile of adipocytes. Interestingly, STAT3 activation in adipocytes correlated with dihomo-γlinolenic acid content and was further induced by arachidonic acid, which conversely down-modulated PPARγ. 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.
Objective: The aims were to collect data on consumption of different food supplements in a sample of the adult Italian population and to characterize users by demographic, physical and health-related characteristics, lifestyle and behaviour. Design: Cross-sectional survey. Setting: The study was conducted in 2008 in ten towns of Italy (two towns from each of the five macro-areas: Northwest, Northeast, Centre, South and Islands). Subjects: Adults (n 10 000) aged $18 years were randomly selected and asked to fill in a self-administered questionnaire regarding their use of food supplements and the above variables. The effect of these variables on food supplement use was evaluated by univariate and multivariate logistic regression. Results: Of the 1723 individuals who returned the questionnaire, 49 % were users of food supplements. A large proportion (54 %) of users used more than one category of food supplement: vitamin and/or mineral supplements were the most used (61 %), followed by supplements with botanicals and botanical extracts (28 %). The results obtained by logistic regression showed that gender, town size, education level, sports practice, regular use of wholemeal cereal-based foods and presence of a low stress level were determinants for the use of food supplements in the examined population. However, these determinants were not shared by all categories of supplements. Conclusions:The results of this preliminary study highlight that associations between demographic, dietary and lifestyle factors and use of different categories of food supplements differ according to products, and cannot be accounted for simply by dichotomizing individuals as users or non-users.
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.
This study shows that when protein requirements are met and there are no remarkable differences between intakes and requirements, there are no repercussions in nitrogen fractions.
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