Abstract
Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.
Highlights
The global incidence of overweight/obesity is expected to reach 20% by 2025 and represents a major health problem, afflicting currently adults and children worldwide [1]
An increase in circulating free fatty acids (FA) have been reported in obesity as a consequence of enhanced release by the enlarged adipose tissue (AT) mass [30,31]. These findings suggest that the altered FA processing and conversion rate can contribute to changing FA profiles in obesity, there is strong evidence that FA content in AT mirrors their relative abundance in the diet
A number of in vitro studies have confirmed the regulatory effects of ω3 polyunsaturated fatty acids (PUFA) on immune homeostasis/inflammation and have highlighted the capacity of the different classes of FA to modulate the biology of human cell populations participating to both innate and adaptive immune responses, and actively involved in tumour surveillance
Summary
The global incidence of overweight/obesity is expected to reach 20% by 2025 and represents a major health problem, afflicting currently adults and children worldwide [1]. Changes in the ω3/ω6 PUFA profile (higher DGLA and docosapentaenoic acid, DPA, versus lower ALA) were reported in SAT from CRC patients in a different study, in association with markers of systemic inflammation [42]. The altered ω3/ω6 PUFA balance in AT and the enrichment in SFA reported in most studies seems to be a common feature of obese and CRC-affected subjects This could markedly affect the function of AT and distal tissues, such as the intestinal epithelium, as a result of an increased ω6 PUFA-mediated inflammation and a reduced protective effect of ω3 PUFA. The changes in FA profiles in different fat depots sustain proinflammatory microenvironment in CRC patients, supporting a role for both unbalanced dietary intake and alterations in FA metabolism and storage in colorectal tumorigenesis
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