Clinical FeaturesEndocrine/Metabolic

Nutrition, Obesity and Cancer Risk

Written by Kathleen A.J. Mitchelson 1 and Helen M. Roche

UCD Conway Institute, Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland and 2 Institute for Global Food Security, Queen’s University Belfast, Belfast, Northern Ireland

Global obesity rates are continuously increasing, having tripled in the last fifty years. Obesity is linked with the occurrence of several co-morbidities including cardiovascular disease, insulin resistance and type 2 diabetes. More recently, obesity has emerged as a major determinate of some cancers. There are at least 13 types of cancer which have a higher incidence rate in those who are overweight or obese, including breast, oesophageal and colorectal cancer. Additionally, individuals who are heavier, with a higher body mass index (BMI) at cancer diagnosis have a higher risk of developing a second, unrelated cancer.

Classic features of obesity include metabolic disease, characterised by high blood glucose levels, insulin resistance and persistent low grade inflammation, collectively termed ‘metabolic inflammation’. Poor diet is a well-known driver of metabolic inflammation. Dietary elements and their digested components either increase or decrease inflammation. However, we are only just beginning to understand how the foods we eat might influence cancer risk. We need to better understand if/how different dietary ingredients can regulate metabolic inflammation when a person develops obesity and consumes a high-fat diet (HFD) within the context of cancer. This will allow for a more complete understanding of the role that obesity has on metabolic inflammation in cancer pathogenesis.


How does obesity and adipose effect inflammation?

The classical hallmark of obesity is the increase in adipose tissue mass. Adipose tissue is where we store excess energy as fat cells. Although adipose tissue was initially thought to just store excess energy, it is now appreciated to have important endocrine functions, secreting cytokines and adipokines which communicate with other cells effecting their behaviour. Adipose tissue is primarily comprised of fat-storing cells called adipocytes, which are surrounded by other cell types that play important roles in human health called the stromal vascular fraction (SVF). SVF is composed of a heterogenous collection of cells including fibroblasts, pre-adipocytes, endothelial cells and immune cells among others. These cells help adipose tissue to communicate with other organs by influencing the signals released. In obesity, the fat cells increase in number and expand in size to store excess energy.

Also, the number of immune cells, T-cells and macrophages in the SVF increase. This increased cell presence disrupts the signalling system and thought to be integral to the development of chronic low-grade inflammation. This haywire signalling from adipose tissue could play an important role in obesity related cancer risk. Generally, inflammation is viewed as a beneficial response of the immune system following injury or infection. However, persistent, non-resolving inflammation is thought to play an important role in obesity related cancer risk.

Is all adipose considered equal?

There are two main adipose (or fat) depots within the body, subcutaneous adipose tissue (SAT) which lies just underneath the skin and visceral adipose tissue (VAT) which lines the internal organs. When adipose storage capacity is exceeded during HFD, fatty acids ‘spill out’ from adipose, increasing circulating free fatty acid concentrations within the blood resulting in accumulation in other peripheral tissues. Fat accumulation in other tissues paired with the increase in the number and activation state of immune cells leads to coordinated modulation and induction of metabolic inflammation. Even though this occurs in both the SAT and VAT depots, the VAT is thought to be the more important source of pathogenic signals.

Does obesity and visceral adipose tissue impact cancer risk?

Whilst it is accepted that obesity is linked to multiple cancer types, potentially contributing to up to 20% of cancer related deaths, exactly how this happens is less evident. Central adiposity, or VAT, seems to be particularly problematic. There are several potential mechanisms wherein the presence of excess visceral adipose mass surrounding the gastrointestinal organs, may promote cancer. Firstly, the increased basal levels of inflammation and this chronic steady state of inflammation may damage or change normal cell behaviour potentially increasing risk of tumour formation. Secondly, obesity may impair the immunosurveillance potential of immune cells to detect aberrant cells for removal. Also, obesity increases the secretion of several hormones, including insulin and insulin-like growth factor 1 (IGF-1) which may trigger cancer development. In addition to promoting carcinogenesis, obesity may also affect the tumour microenvironment through reduced anti-tumour immunity preventing disease resolution.

Importance of obesity and specific adipose tissue depots are evident in the risk and progression of gastrointestinal cancers, specifically oesophageal and colorectal cancer. VAT of non-cancer, non-obese cancer and obese cancer patients have been studied. Interestingly, noncancer and non-obese cancer patients VAT characteristics were similar in the ability to decrease cell growth rate and invasiveness in oesophageal adenocarcinoma cancer (OAC). Alternatively, VAT from obese cancer patients displayed an enhanced pathogenic response in OAC cells. Additionally, an increase specifically in VAT mass is positively associated with colorectal cancer (CRC) prevalence in both men and women. VAT signals may advance tumour progression through possible pro-inflammatory/lipid pathway alterations. If that is in fact the case, the question would be could adipose biology be re-programmed to reduce cancer risk? The relationship between cancer and obesity has reinforced the importance of nutrition in gastrointestinal cancers. Current research is actively investigating the different mechanisms that explain if / how diet related obesity either triggers the initiation or promotes the progression of different cancers.

Dietary Modulators of Metabolic Inflammatory Disease

Obesity is attributed to excess energy intake but not all energy is considered equal with some nutrients being more deleterious than others. Recent work from our team, and others, demonstrate that dietary elements, including dietary fatty acids, can have differential impacts on adipose tissue profile, metabolism and inflammation. Dietary fatty acids differ in their health effects. Saturated fats (SFA) have no double bonds in their carbon backbone while monounsaturated fats (MUFA) have one double bond. Diets high in SFA (e.g. those rich in processed foods enriched in palm oil, coconut oil) induced a very adverse hypertrophic adipose profile consisting of larger adipocyte cell size and insulin resistant state. In contrast, MUFA (e.g. typically found in olive oil as part of the Mediterranean diet) do not, despite equal obesity. Diets high in MUFA instead result in a healthier more functional, hyperplasia adipose profile which is an increase in adipocyte cell number. Usually feeding a HFD rich in SFA increases the secretion of pro-inflammatory cytokines such as interleukin – 1β (IL-1β). IL-1β is a predominant proinflammatory cytokine in obesity, metabolic disease and cancer. However our work suggests that IL-1β inflammation maybe impacted by the type of dietary fats in the diet. Macrophages secrete less IL-1β following stimulation when fed a diet high in MUFA, compared to a SFA rich diet. Distinct fatty acids elicit individual effects on metabolic inflammation. Replacement of SFA with MUFA may represent a dietary intervention strategy to dampen HFD mediated metabolic inflammation. Furthermore, adipose hypertrophy within the visceral adipose tissue produces a greater risk of both metabolic risk, OAC and CRC (Figure 1). We are interested in investigating if feeding different fats can alter the risk of diet induced obesity and OAC/CRC risk.


It is probable that diet directly impacts the health and progression towards obesity, metabolic disease and cancer. A greater understanding of the mechanisms behind the different dietary elements driving disease progression are necessary. Novel dietary interventions may be useful as a supplementary treatment approach to manage and/or prevent cancer progression.


K.A.J.M. and H.M.R. are funded by Precision Oncology Ireland (18/SPP/3522), a Science Foundation Ireland Strategic Partnership Programme.

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