In both clinical and epidemiological research, obesity and weight gain is increasingly being linked to systemic inflammation. This inflammatory condition is caused by the accumulation of white adipose tissue, that subsequently attracts macrophages which infiltrate the tissue and cause the release of pro-inflammatory cytokines. The systemic inflammation associated with weight gain is thought to be the cause of the increased risk of a number of other obesity related diseases including diabetes and cardiovascular disease. An increased risk of cancer of the colon is also associated with obesity, and mouse models show that feeding the Western diet to mice causes obesity followed by inflammation and oxidative stress in the colon. Cytokines related to white adipose tissue such as tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) might therefore stimulate the epithelial cells of the colon causing colorectal adenomas which ultimately lead to cancerous tumours.
Researchers1 have measured inflammation and gene expression in colon biopsies of 10 obese women before and after diet induced weight loss. Subjects lost 8% of their bodyweight by following a very low-calorie diet. Following weight loss the subjects had significantly lower fasting blood glucose, total cholesterol, triglycerides, LDL-cholesterol levels, as well as reduced concentrations of plasma TNF-α and IL-6. Biopsies of colon tissue showed that a number of cytokines had been reduced in concentration compared to baseline (TNF-α, IL-6, IL-8 and monocyte chemotactic protein-1) by between 25 to 57%. There was also a significant reduction in the expression of genes relating to pro-inflammatory pathways (eicosanoid, cytokine, chemokine and the transcription factors nuclear factor κβ and STAT3). Weight loss also caused a reduction in the expression of the FOS and JUN genes, transcription factors ATF and CREB, and down regulated oxidative stress pathways.
These results suggest that weight loss is associated with a decrease in systemic inflammation and oxidative stress. The subjects in this study were administered a very low calorie diet that was maintained until 8% of body weight had been lost. However, no effort was made to increase the quality of the diet, something that may have produced an even greater effect on inflammation and oxidative stress. The fact that aspirin is known for its anti-inflammatory effects and is able to reduce the risk of colorectal adenomas supports the theory that inflammatory and oxidative stress mechanisms may be involved in their development. Aspirin is also reported to work more effectively in subjects with greater body weight which further supports this idea. These results show a possible link between obesity and cancer and provide further evidence to suggest that the ill-health associated with obesity is caused by inflammation and oxidative stress.