Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis

Abstract

Due to its prevalence, obesity is now considered a global epidemic. It is linked to increased risk of colorectal cancer, the third most common cancer and the second leading cause of death among adults in Western countries. Obese adipose tissue differs from lean adipose tissue in its immunogenic profile, body fat distribution and metabolic profile. Obese adipose tissue releases free fatty acids, adipokines and many pro-inflammatory chemokines. These factors are known to play a key role in regulating malignant transformation and cancer progression. Obese adipose tissue is infiltrated by macrophages that participate in inflammatory pathways activated within the tissue. Adipose tissue macrophages consist of two different phenotypes. M1 macrophages reside in obese adipose tissue and produce pro-inflammatory cytokines, and M2 macrophages reside in lean adipose tissue and produce anti-inflammatory cytokines, such as interleukin-10 (IL-10). The metabolic networks that confer tumour cells with their oncogenic properties, such as increased proliferation and the ability to avoid apoptosis are still not well understood. We review the interactions between adipocytes and immune cells that may alter the metabolism towards promotion of colorectal cancer.

Impact of Body Mass Index on the Risk of Colorectal Adenoma in a Metabolically Healthy Population

“…The mechanisms that link increased BMI and CRA are not fully understood, although several possibilities have been raised (3,27,28). Insulin resistance is considered a key mechanism underpinning the obesity-colon cancer link (3,27).…”

Serum concentrations of brain-derived neurotrophic factor (BDNF) are decreased in colorectal cancer patients

“…Sporadic CRC is linked to multiple environmental risk factors, with obesity consistently demonstrated to be a significant and independent risk factor [25,26]. BDNF has been shown to have a key role in energy homeostasis and the regulation of appetite and food intake control [27].…”

Melatonin reduces obesity and restores adipokine patterns and metabolism in obese ( ob/ob ) mice

“…Over the past decade, profound changes in nutrition and lifestyle have led to a sharp increase in the prevalence of obesity and its complications. Actually, it has reached epidemic proportions in many parts of the world and this trend is expected to continue [1,2].…”