How is obesity linked to cancer?

According to the World Health Organization (WHO), obesity is considered a possible cause of at least 13 different types of cancer and may even replace smoking as the main preventable cancer risk in some regions of Europe [Calle and Kaaks, 2004; World Health Organization, 2022]. The biological mechanisms underlying the link between obesity and cancer are not fully understood. However, hormonal changes, such as sex hormones or insulin secretion, as well as chronic inflammation in adipose tissue and impairment of the immune system are thought to play a role [Renehan et al., 2015; Murphy et al., 2018; World Health Organization, 2022].

The Max Planck Institute for Metabolism Research is intensively investigating the link between obesity and cancer. In particular, researchers are focusing on obesity-related metabolic inflammation in two types of cancer: hepatocellular carcinoma (liver cell cancer) and colorectal cancer (bowel cancer).

Liver cell cancer

Hepatocellular carcinoma (HCC), also known as liver cell cancer, is a malignant change in liver cells [Mittenbühler et al., 2020]. Worldwide, HCC is the fifth most common cancer and the third most common cause of cancer death [Bornschein et al., 2016]. A combination of insulin resistance, hypertension, dyslipidaemia and obesity - known as the metabolic syndrome - is increasingly recognised as a cause of HCC, alongside hepatitis B or C disease [Siegel et al., 2009].

The Max Planck Institute for Metabolism Research has now shown in experiments with mice that obesity induced by a high-calorie diet actually favours the development of liver cell cancer [Gruber et al., 2013].

At our institute, the Max Planck Research Group Wunderlich conducts research into liver cell cancer.

Bowel cancer

Obesity is also an important risk factor for bowel cancer, also known as colorectal cancer. Approximately 11% of colorectal cancer cases in Europe can be attributed to overweight and obesity [Bardou et al., 2013].

On the one hand, obesity-related colorectal cancer is associated with changes in the microflora [Schulz et al., 2014]. On the other hand, studies from the Max Planck Institute for Metabolism Research have revealed another possible cause for the development of colorectal cancer in relation to obesity. In experiments in which obese mice had a higher rate of bowel cancer tumours than lean mice, an accompanying inflammatory response was also identified. This inflammation correlated with tumour formation. Scientists at the Institute now suspect that inflammatory messengers promote the development of bowel cancer.

At our institute, the Max Planck Research Group Wunderlich conducts research into bowel cancer.

Inflammation sends out messengers

The increase in white adipose tissue caused by obesity leads to stress in the fat cells, which activates immune cells and recruits them to the adipose tissue. This leads to the release of certain messengers called cytokines [Kern et al, 2019]. Cytokines are signalling molecules that enable communication between different cells and regulate immune responses [Robert Koch-Institut, 2004]. They can have both anti-inflammatory and pro-inflammatory effects [Wautier & Wautier, 2023].

Two known pro-inflammatory cytokines associated with obesity are interleukin-6, or (IL)-6, and tumour necrosis factor α, or TNFα [Weisberg et al., 2003]. The release of these cytokines by immune cells in inflamed adipose tissue leads to the recruitment of other immune cells, which not only promote local inflammation but are also released systemically through the bloodstream [Xu et al, 2003]. Chronic inflammation associated with obesity thus impairs insulin sensitivity in all metabolic organs and may also promote the development of hepatocellular carcinoma and colorectal cancer [Kern et al., 2019].

What is metabolism?

What is overweight? What is obesity?

Why are more people becoming obese?

Which neural circuits are involved in metabolism?