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Page 2 of 12 Conti et al. J Cancer Metastasis Treat 2019;5:64 I http://dx.doi.org/10.20517/2394-4722.2019.015

Keywords: Obesity, adipose tissue, inflammation, diet, weight loss, fatty acids, colorectal cancer

INTRODUCTION
The overweight and obesity epidemic represents a rapidly growing health threat in several countries. Excess
adiposity is associated with increased incidence of several cancers and represents an important indicator of
survival, prognosis, recurrence and response to therapy in many tumors, including colorectal cancer (CRC).
The risk of developing CRC is significantly increased in obese subjects, with abdominal obesity being more
[1]
predictive than overall obesity, and is highly modifiable by diet . Dietary habits and excessive adiposity can
[2]
not only influence cancer growth but also shape host immune response . White adipose tissue (AT), now
[3]
recognized as the largest endocrine organ, plays a key role in metabolic and immune homeostasis . This
tissue influences many local and systemic physiological and pathological processes by virtue of its capacity
to secrete a large number of hormones, cytokines/chemokines/adipokines, extracellular matrix proteins,
[4]
lipid metabolites and growth factors . In condition of chronic positive energy balance, AT undergoes
profound modifications including adipocyte expansion, induction of hypoxia, and mitochondrial function
[5]
alterations that lead to tissue remodeling, inflammation and metabolic dysfunction . These events tightly
[6,7]
couple with dramatic changes in the immune cell repertoire and functions shifting the balance of cell
subsets and soluble mediators toward a pro-inflammatory profile. Indeed, growing evidence indicates that
meta-inflammation - a chronic low-grade inflammatory state occurring in metabolically active tissues
including the AT - characterizes obesity and contributes to the impairment of immune functions, thus
[8]
representing a key determinant in the development of obesity-related morbidities, including cancer .
Evidence suggests that lipids, especially fatty acids (FA), the main components of AT, play an important
role not only in obesity development but also in the interplay between excessive adiposity and development
[9]
of associated diseases . Dietary lipids derived from plants and animals encompass FA (saturated, SFA,
monounsaturated, MUFA, and polyunsaturated, PUFA), their derivatives including mono-, di-, and
triglycerides and phospholipids, as well as sterols such as cholesterol. Among FA, SFA are mainly found in
animal food, but a few plant food is also high in saturated fats, such as coconut, coconut oil, palm oil, and
palm kernel oil. MUFA can come from both various plant-based (e.g., vegetable oils and nuts) and animal-
based sources (e.g., red meats and high-fat dairy products). PUFA are essential FA as they cannot be
synthesized from precursors in the diet, and derive primarily from plant-based sources. However, ω3 PUFA
can also be found in fish oils [10,11] .

The type of FA stored in AT, besides adipocyte fat overload, critically affects tissue functions. FA can
directly or indirectly modify immune and inflammatory responses by several mechanisms, acting on
cell surface and intracellular receptors that control cell signaling and gene expression [12,13] . Recent studies
have indicated that dietary FA quality rather than quantity has major implications in meta-inflammation
development. In fact, FA exhibit either pro- or anti-inflammatory activity depending on their chemical
structure [11,13] . In general, long-chain SFA have been associated with inflammation while short-chain FA
[14]
show anti-inflammatory effects . On the other hand ω3 PUFA favor anti-inflammatory profiles, while ω6
[10]
PUFA, with a few exceptions, are endowed with pro-inflammatory activity . Lastly, the effect of MUFA is
more debated, with evidence for either anti-inflammatory or weak pro-inflammatory responses [11,13] .

The FA composition of AT is widely considered a marker of medium- and long-term dietary fat intake,
[15]
with a general agreement that FA content in AT mirrors their relative abundance in the diet . However,
FA profile in AT also depends on, at a certain extent, a metabolic control. Indeed, different AT sites
[19]
[18]
exhibit different FA compositions [16,17] as well as different rates of FA turnover and active remodeling .
Furthermore, while some ω3 PUFA such as decosahexaenoic acid are preferentially stored, others like