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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 3 of 12
[19]
eicosapentaenoic acid are preferentially released or turned over during lipolysis . More recently, evidence
points to a relevant role of enzymes involved in FA metabolism in defining plasma and tissue FA profiles.
Human studies indicate that inter-individual variation in desaturase genes is due to both genetic and
[20]
lifestyle factors, highlighting that the function of these enzymes may influence disease risk .
In the following sections we will overview obesity-, diet-, and weight loss-associated changes of FA profiles
by focusing on human AT. The role of FA as potential regulators of inflammation in metabolically active
tissues, in particular AT, and as a link between obesity and CRC development will be discussed.

OBESITY-ASSOCIATED FATTY ACID PROFILES OF ADIPOSE TISSUE AND THEIR
RELATIONSHIP WITH DIETARY INTAKE
Subcutaneous (SAT) and visceral (VAT) white AT depots constitute AT bulk. Their body distribution
shows person-to-person variations and depends on several factors such as age, nutrition, sex, and
[21]
energy homeostasis of the individual AT . VAT and SAT show significant variations in anatomical,
[22]
cellular, molecular, and physiological characteristics and play different roles in metabolic syndrome
[21]
development . In fact, excessive VAT accumulation is commonly associated with insulin resistance,
markers of oxidative stress and inflammation, high risk of type 2 diabetes (T2D), dyslipidemia, and high
mortality [23-25] . Conversely, SAT accumulation is associated with improved insulin sensitivity and lower
risk of T2D. Furthermore, metabolically beneficial adipokines (i.e., leptin and adiponectin) are secreted
in higher amounts by SAT, whereas pro-inflammatory mediators are more abundantly secreted by VAT,
[22]
regardless the body weight . Interestingly, in obese subjects, SAT exhibits a higher content of SFA with
respect to VAT that instead shows a higher accumulation of MUFA as well as a higher activity of stearoyl-
coenzyme A desaturase 16 (SCD16) and SCD18. Conversely, a similar PUFA composition has been
reported for both fat depots [16,17] .

Some studies investigated obesity-associated FA profile of AT that can be modified by specific diets, weight
loss or in pathological conditions like CRC. However, the patterns of FA accumulation distinguishing lean
with respect to obese subjects are poorly known. A summary of the main differences in FA profiles of AT
related to fat depot, obesity, weight loss and cancer, are shown in Table 1.

Despite any difference in SFA, MUFA and PUFA (ω3 and ω6) total content in the VAT of lean with respect
[26]
to obese subjects, a clear-cut decrease in the ω3/ω6 ratio was detected in the latter . Furthermore, analysis
of individual members of the ω6 PUFA family unraveled that arachidonic acid content increases in obese
subjects with respect to lean while γ linolenic acid, the only member of the ω6 PUFA family endowed with
[27]
anti-inflammatory activity, decreases in the same subjects . Moreover, a higher palmitoleic acid content
[28]
and SCD1 index have been reported in SAT of obese vs. lean subjects . Likewise, our study demonstrated
that higher levels of palmitoleic and stearic acids together with a higher desaturation index (i.e., SCD1 Δ9-
[29]
18) are found in the VAT of obese subjects .

The FA composition of AT reflects not only the dietary intake but also endogenous fat processing. Thus,
changing the nature of the fat consumed has a profound influence on the type of FA available to the
[30]
body and may alter AT composition . In this regard, our most recent data show a higher arachidonic
acid dietary intake in obese subjects as well as a higher arachidonic acid content of VAT [27,29] . The relative
proportion of some PUFA (i.e., linoleic, α linolenic, eicosapentaenoic and decosahexaenoic acids) as well as
of SFA (i.e., palmitic acid) and MUFA (i.e., palmitoleic acid) in SAT was also found to mainly reflect their
[31]
dietary intake in a large Swedish cohort study of adult men . Likewise higher levels of oleic acid in SAT
[32]
were observed when overweight subjects received a MUFA- rather than a SFA-rich diet .The association
between dietary FA and their composition in specific AT was studied in a cohort of obese subjects from the