Page 71 - Read Online

Page 6 of 12 Conti et al. J Cancer Metastasis Treat 2019;5:64 I http://dx.doi.org/10.20517/2394-4722.2019.015
[44]
a role for VAT PUFA composition in shaping immune phenotypes . ω3 and ω6 PUFA, in particular
decosahexaenoic and arachidonic acids, have also been reported to differently influence adipocyte
transcriptional program in lean and obese subjects [42,43,45] . Among the genes modulated by decosahexaenoic
acid are those involved in AT inflammation and metabolism such as FADS1 and FADS2 genes that code
for D5D and D6D, respectively, and thus control AT PUFA metabolism [45,46] . The regulatory action of
dietary PUFA on adipocyte genomics adds further evidence for a role of diet in the modulation of obesity-
associated AT inflammation.

The role of FA in the modulation of obesity-associated AT inflammation has also been investigated in
several clinical trials aimed at assessing the effect of consumption of different FA on the expression of
inflammation-related genes in AT. However, some conflicting results have been reported probably due
to the large variability in concentration and type of FA used in each intervention, differences among the
specific populations investigated, variability in intestinal microbiota among individuals. Moreover, recent
studies suggest that the AT response to FA is more complex than originally anticipated, and that the gene
expression in AT is site specific suggesting that not all fat depots in the body are controlled in the same
manner. The analysis of inflammatory responses in different sites (SAT or VAT, whole AT or isolated
adipocytes) may therefore have generated discordant results.

As described for the in vitro studies, the consumption of a SFA-rich diet results in a pro-inflammatory
gene expression profile in SAT (i.e., CD16a, IL-1β, IL-6, IL-6R and TNF-α), while MUFA-rich diet or
acute post-prandial MUFA intervention lead to different profiles depending on the category of subjects.
[32]
Indeed in abdominally obese or healthy subjects the majority of regulated genes show anti-inflammatory
features, whereas in subjects at higher risk of T2D the post-prandial consumption of MUFA-containing
macadamia nut oil evokes an inflammatory response with up-regulation of several inflammatory genes
[47]
(CCL2, IL-1β,IL-6, IL-6R, TNF-α and TNFRSF1A) . These results indicate that MUFA can also exert a
pro-inflammatory response, which is greater among subjects with obesity-related diseases as compared to
healthy individuals. In line with this evidence, an exacerbated AT post-prandial inflammatory response
[48]
(NF-κBp65, CCL2, IL-6 and IL-1β) occurs in SAT of metabolic syndrome patients .

The potential benefits of ω3 PUFA consumption on a wide range of AT inflammatory responses have
[49]
been highlighted in recent studies . In a randomized controlled trial involving severely obese patients
(≥ 40 kg/m ), ω3 PUFA supplementation over an eight-week period results in down-regulation of
2
inflammatory genes (CCL2, CCL3, HIF1Α, CD40 and IL-6), and up-modulation of the anti-inflammatory
[50]
adiponectin in SAT, but not in VAT, in comparison with the control group . Additionally, consumption of
different sources of fatty fish reduces the expression of AT inflammatory genes including inflammasome-
associated IL-18, IL-1β and IL1RN or impairs fasting glucose in obese subjects [43,51] . Moreover, in a clinical
trial (FFAME) involving healthy volunteers and based on eicosapentaenoic and decosahexaenoic acid
supplementation, ω3 PUFA showed immune-modulatory and anti-inflammatory capability through
the modulation of several inflammatory and specific immune genes during evoked AT inflammation
induced by experimental endotoxemia [52,53] . In contrast to these results, no effect on SAT inflammation
[54]
was observed neither in overweight to moderately obese adults consuming a diet rich in ω3 PUFA , nor
[55]
in obese postmenopausal women after decosahexaenoic acid supplementation . Finally, ω3 PUFA (i.e.,
eicosapentaenoic acid and/or α-lipoic acid) dietary supplementation in addition to weight loss and dietary
interventions unravels differences in the expression of genes related to inflammation and immune response
[56]
in SAT from overweight/obese women . Other clinical evidence demonstrates that weight loss, known to
improve obesity-associated low grade inflammation, is linked to changes in AT FA composition, suggesting
[57]
a specific role of different FA in weight management and control of inflammation .

A strong association between SFA and MUFA AT profiles and AT inflammation was demonstrated by
the KOBS study. The results achieved showed that surgery-induced weight loss of obese individuals