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Conti et al. J Cancer Metastasis Treat 2019;5:64 I http://dx.doi.org/10.20517/2394-4722.2019.015 Page 7 of 12

reduces the expression of IL-1β and NF-κB pathway and unravels a positive/negative association between
[16]
inflammation and SFA and MUFA content, respectively, in both SAT and VAT . These correlations were
modified by the FADS1/FADS2 genotype, both in KOBS and DIOGENES studies, indicating that variants
in this gene cluster may influence the interaction between AT FA and tissue inflammation [16,58] . In the
[38]
same KOBS cohort, Walle et al. measured serum and AT FA composition and AT expression of genes
regulating FA metabolism before and one year after obesity surgery, combined with dietary counseling.
Interestingly, some of the changes observed in AT FA profile are associated with the expression of elongases
[38]
and desaturases, key enzymes in FA metabolism . According to these results, weight loss after bariatric
[59]
[60]
surgery in morbidly obese women or after LCD in obese premenopausal women significantly
improves the SAT inflammatory and immune profile by decreasing the expression of pro-inflammatory
factors while increasing that of anti-inflammatory molecules as well as of genes involved in the regulation
of lipid metabolism. Furthermore, the effects of two different LCD among obese women, within the
NUGENOB study trial, were determined on SAT mRNA expression level, according to energy deficit and
[61]
fat to carbohydrate ratio . Among the transcripts deregulated during the diets are genes involved in lipid,
carbohydrate and energy metabolism [61,62] . In contrast to these results, no changes in adipocyte gene related
to inflammation and metabolism were reported in SAT in two cohorts of obese pre- and post-menopausal
women after energy-restricted diets [63,64] , although inflammation related biomarkers were reduced
[63]
systemically .

ADIPOSE TISSUE INFLAMMATION, FATTY ACID PROFILE AND COLORECTAL CANCER
AT-associated inflammation promoted by incorrect dietary habits and obesity, under the influence of
signals derived from the gut microbial flora, is a main mechanism that may favor CRC development and
[65]
progression . Inflamed AT may contribute to tumorigenesis by releasing pro-inflammatory mediators
and by modifying the lipid metabolism, which is part of the reprogrammed energy metabolism that
[66]
characterizes cancer . In turn, cancer cells have the ability to induce metabolic changes in neighboring
adipocytes and to use AT released FA as substrates for their proliferation [67,68] .

A number of studies have analyzed the profiles of FA in AT of CRC patients, in association or not with
dietary intake, or have correlated specific FA profiles with CRC risk [69,70] . Some old studies reported a
similar FA profile in healthy and CRC affected subjects [71,72] . However, despite a comparable consumption
of the major dietary components and fat intake between the study groups, an age-associated decrease in
unsaturated fat intake was observed only in the CRC group. Conversely, correlation between dietary and
[72]
AT PUFA:SFA ratio was found in the control but not in the cancer group .
More recently, a general agreement has been achieved on the increased accumulation of pro-inflammatory
ω6 PUFA (mostly dihomo-γ-linolenic and arachidonic acids) as well as on the unbalanced ω3/ω6 PUFA
ratio in the AT of CRC patients, regardless of tumor subsite, even though differences were reported among
studies on the relative abundance of individual PUFA and type of AT involved [27,73-75] . In particular, a
comparison of VAT and SAT FA profiles in colon cancer (CC) patients highlights a decrease of the ω3
PUFA α linolenic and stearidonic acid content, coupled to increased dihomo-γ-linolenic and arachidonic
acid content in VAT of CC patients as compared to controls. Conversely, FA composition of SAT in
[74]
CC subjects is only marginally altered, with increased γ linolenic acid levels . Although no dietary
information was available for the study population, the low ω3/ω6 PUFA ratio generally observed in AT
[74]
likely reflects Western dietary habits . Changes in the ω3/ω6 PUFA profile (higher dihomo-γ-linolenic
and docosapentaenoic acids, vs. lower α linolenic acid) were also reported in SAT from CRC patients, in
[75]
association with markers of systemic inflammation . The altered ω3/ω6 PUFA balance in cancer patients
can markedly affect tissue composition and function as a result of the reduced protective effect of ω3
PUFA. Moreover, a CRC-associated increase of total SFA and MUFA content in VAT and SAT, respectively,
[74]
was also described in some studies .