Fat Mice Get Bigger Tumors

It is well known that obesity increases the risk for various forms of cancer.  A National Cancer Institute fact sheet on the obesity-cancer link provides useful information on this topic, as does another information source from Cancer Research UK.

Mouse models of human cancer are often used to investigate the mechanisms of the human disease. A recent paper in the journal Oncotarget (free online) demonstrates that even in mice, obesity due to a high fat diet increases the development of cancer, in this case, colon cancer.  Thus, colon cancer cells injected into the mice resulted in larger tumors when the mice were fed a high fat diet.  The abstract of the paper is as follows:

There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that mice fed a high-fat diet (HFD) and injected with MC38 colon cancer cells develop significantly larger tumors than their counterparts fed a control diet. In ex-vivo experiments, MC38 and CT26 colon cancer cells exposed to conditioned media (CM) from the adipose tissue of HFD-fed mice demonstrated significantly lower oxygen consumption rate as well as lower maximal oxygen consumption rate after carbonyl cyanide-4-trifluoromethoxy-phenylhydrazone treatment. In addition, in-vitro assays showed downregulated expression of mitochondrial genes in colon cancer cells exposed to CM prepared from the visceral fat of HFD-fed mice or to leptin. Interestingly, leptin levels detected in the media of adipose tissue explants co-cultured with MC38 cancer cells were higher than in adipose tissue explants cultures, indicating cross talk between the adipose tissue and the cancer cells. Salient findings of the present study demonstrate that this crosstalk is mediated at least partially by the JNK/STAT3-signaling pathway.

Mitochondria are the “powerhouse of the cell,” responsible for generating most of the ATP that provides the “chemical energy” the cells require, and mitochondria are involved in other important processes, such as programmed cell death. This paper shows that diet-derived obesity causes the mitochondria to malfunction and this contributes to increased tumor formation.  An important cell signaling pathway called JNK/STA3 is apparently involved in the association between obesity and cancer in these over-fed mice. The authors conclude:

We conclude from this study that (i) obesity induces mitochondrial dysfunction, promoting cancer in several organs adjacent to the visceral fat, such as the colon, and (ii) inhibition of the JNK/STAT3-signaling pathway in colon cancer cells seems to be critical for reestablishing mitochondrial function and overcoming the glycolytic phenotype. We assume that this signaling pathway may be partly responsible for the relation between obesity–leptin-induced mitochondrial dysfunction and colon cancer.

What does this mean for the typical person, who may not be familiar with all the scientific jargon used? This paper is yet more evidence of the serious damage done to the organism by diet-induced obesity, damaging the mitochondria and affecting signaling in many cells, and these negative effects contribute to cancer development. What is happening in these mice likely occurs in people as well. Losing weight to transition to a more normal BMI – and optimally, never becoming obese to begin with – must rank as one of the most important things you can do for your health. And of course, the benefits are not only restricted to cancer, but to cardiovascular diseases, metabolic diseases (e.g., diabetes), and much more.

The mice in this study didn’t have a choice about their obesity, they do not have the capacity to understand the diet they were given, and the effects that diet had on their bodies. We in contrast do understand and do have a choice, and we need to choose wisely.