Link Between High Fat Diets and Colon Cancer
A high-fat diet is unhealthy and promotes the development of colon cancer. But what exactly increases the risk of colon cancer and which mechanisms in the diet with high-fat foods play a role here?
A new study involving researchers from Arizona State University has now found that a high-fat diet triggers three factors in particular that increase the risk of colon cancer. The study was published in the journal “Cell Reports” released.
Obesity promotes the development of tumors
“There is epidemiological evidence of a strong association between obesity and an increased risk of cancer. In the intestine, the stem cells are the probable source cells for cancer, ”explains study author Miyeko Mana. But what is the connection?
Diet is something that affects this cycle of obesity and colon cancer, and the new study has shown more precisely than ever how a high-fat diet triggers a molecular cascade of events that lead to colon cancer, the researchers explain.
What role do intestinal stem cells play?
As foods break down in the body and make their way through the intestines, they interact with intestinal stem cells (ISC), which are positioned along the inner surfaces of the intestine. These stem cells are located in invaginations of the intestine, which are also known as intestinal crypts.
ISCs are believed to act as a kind of gateway that coordinates the formation of colon tumors when they adapt to a high-fat diet, the team reports. Inside the ISC there are fat-rich sensor molecules, which sense the content of fat-rich food in the cells and react to it.
PPARs can increase cancer risk
“We were investigating the mechanisms that might be necessary for the adaptation of stem cells to the high-fat diet – and that’s where we came across PPARs,” explains Mana. These so-called peroxisome proliferator-activated receptors (or PPARs) trigger a cellular program that increases the risk of cancer. But the exact mechanisms have so far remained unclear because there are several types of PPARs and it is difficult to determine their exact role.
“There is a family of three PPARs called Delta, Alpha, and Gamma. At first I thought that only PPAR delta was involved, but to see whether this gene is really responsible for the phenotype, you have to remove it, ”explains the expert. The team actually succeeded in determining the role of the individual PPAR delta and alpha with the help of a mouse model, which controlled their activity in the cell.
Animals were given a long-term high-fat or normal diet for the study, and the activity of each PPAR was carefully monitored to assess the effect on cancer risk.
First, the experts removed the PPAR-delta gene. “But when we removed it from the intestines, we were still observing the phenotype. So we wondered if maybe another PPAR would compensate, and that’s when we thought of PPAR alpha. Both (PPAR delta and PPAR alpha) seem to be required for this high-fat diet phenotype in the stem cells, ”explains Mana.
“So we took a closer look at what these two factors (PPARs) might be targeting, and that was the mitochondrial protein Cpt1a. This is required for the import of long chain fatty acids (LCFAs) into the mitochondria for use. The LCFAs are part of the high-fat diet, ”continues Mana.
Removal of Cpt1a reduced risk of tumorigenesis
When the researchers carried out a study on Cpt1a on mice, they found that they could stop tumor formation in their pathways. The loss of Cpt1a prevented both the expansion and the proliferation of the ISCs in the crypts. “If you remove Cpt1a, you are spared this high-fat diet phenotype in the intestinal stem cells. So at this point you lower the risk of tumorigenesis, ”says Mana.
For example, a high-fat diet leads to cancer
Based on the data, the development of cancer from diet to tumor formation could be traced. First, fats are broken down into free fatty acids. The free fatty acids then stimulate sensors such as the PPARs and switch on genes that can break down the fatty acids.
Next, the excess free fatty acids are transported to the mitochondria, which can burn them through oxidation to generate more energy for the stem cells to multiply, grow and regenerate the intestinal tissue. But if the number of ISCs is increased, there is a greater chance that mutations can occur – simply due to random mutations and the sheer number of cells that lead to colon cancer, the team explains.
“The idea is that this larger pool of cells will stay in the gut and accumulate mutations, and that means they can be a source of mutated cells that lead to transformation and tumor initiation. We think that this is a likely possibility if there are conditions that expand the stem cell pool, ”the experts speculate.
High fat diets greatly accelerated mortality
The team found that a high-fat diet dramatically shortened life expectancy in this model compared to the control condition by allowing for faster tumorigenesis.
This is how the bowel can be healed
“The amount of these fats that you can eat through your diet will affect your stem cells, probably in a fairly straightforward way,” explains Mana in one Press release from Arizona State University. The expert found it quite surprising that fatty acids can have such a direct effect. But if these PPARs and CPT1a are removed, the intestine will be healthy again.
“So far, these studies have all been carried out in these mouse models. One idea we started with was to understand the metabolic dependencies of tumors that can arise in a natural or pharmacological context, and then manipulate those metabolic programs to the detriment of the tumor, but not normal tissue. We are making progress with the high fat diet model. Ultimately, however, the goal is to eliminate or prevent colon cancer in humans, ”sums up Mana. (as)
Author and source information
This text complies with the requirements of specialist medical literature, medical guidelines and current studies and has been checked by medical professionals.
- Miyeko D. Mana, Amanda M. Hussey, Constantine N. Tzouanas, Shinya Imada, Yesenia Barrera Millan et al.: High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity, in Cell Reports (veröffentlicht 08.06.2021), Cell Reports
- Arizona State University: Study shows new links between high fat diets and colon cancer (veröffentlicht 09.06.2021), Arizona State University
This article is for general guidance only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor.