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Review
. 2016 Aug:29:77-89.
doi: 10.1016/j.coph.2016.07.005. Epub 2016 Jul 16.

Obesity and cancer: inflammation bridges the two

Ryan Kolb  1 , Fayyaz S Sutterwala  2 , Weizhou Zhang  3
Affiliations
Review

Obesity and cancer: inflammation bridges the two

Ryan Kolb et al. Curr Opin Pharmacol. 2016 Aug.

Abstract

Obesity is a growing public health problem and affects 35% US adults. Obesity increases the risk of many cancer types and is associated with poor outcomes. Clinical management of cancer patients has been essentially the same between normal weight and obese individuals. Understanding causal mechanisms by which obesity drives cancer initiation and progression is essential for the development of novel precision therapy for obese cancer patients. One caveat is that various mechanisms have been proposed for different cancer types for their progression under obesity. Since obesity is known to have global impact on inflammation, here we will summarize recent literature and discuss the potential of inflammation being the common causal mechanism to promote cancer promotion across cancer types.

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Figures

Figure 1
Figure 1. Obesity promotes breast cancer
Obesity leads to macrophage infiltration and inflammation in white adipose tissue in the breast. This is associated with the upregulation of several pro-inflammatory and pro-tumorigenic cytokines. Inflammatory cytokines can promote the upregulation of aromatase and increased production of estrogens in stromal cells of the breast. Obesity-associated inflammation is also involved in the development of insulin resistance and increased IGF-1, which is a mitogen for breast epithelial cells. Obesity also leads to an increase in leptin and a decrease in adiponectin. Leptin expression is induced by inflammatory cytokines and can induce expression of inflammatory cytokines leading to increased inflammation. Leptin can promote breast cancer through increased proliferation, survival and angiogenesis. All of these factors likely contribute to a pro-tumorigenic microenvironment that promotes breast cancer.
Figure 2
Figure 2. Obesity and colorectal cancer
Obesity is associated with changes in the intestinal microbiome and dysfunction of the intestinal barrier. Gut dysbiosis and endotoxemia promotes inflammation through the upregulation inflammatory cytokines, particularly IL-6, TNF-α, IL-17 and IL-23, which promote CRC carcinogenesis. Obesity-associated changes in leptin and adiponectin also leads to increased inflammation and CRC carcinogenesis.
Figure 3
Figure 3. Obesity and liver cancer
The development of liver cancer in obese patients is associated with chronic liver damage and NAFLD. Obesity leads to an accumulation of triglycerides in the liver (hepatic steatosis), which leads to increased free fatty acids and other lipid metabolites and in turn to hepatocyte cell death and regeneration. This process is associated with liver inflammation. Upregulation of leptin and down regulation of ATG7 result in decreased autophagy that leads to increased inflammation and oxidative stress. Gut dysbiosis and endotoxemia leads to increased inflammation. Cycles of liver damage and regeneration and the associated inflammation creates a microenvironment that promotes the development liver cancer.
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