Lean meat can cause colon cancer-what you need to know about a high-fat diet and cancer

The more lean meat you eat, the more likely you are to get colorectal cancer, so you may want to replace the steak with a pea salad. Health officials have urged people for years to limit their intake of lean meat, as it can lead to many illnesses such as heart disease and cancer. Lean meat includes beef, pork and mutton. New research reveals how a high-fat diet triggers molecular cascade events that lead to gut and colon cancer. The results of this research were published in the magazine “Cell Reports”. Read again- Avoid these five common foods that can weaken your immune system

Colorectal cancer is the seventh most common cancer diagnosed in both men and women in India. The causes of colon cancer are multifactorial and complex. According to the Centers for Disease Control and Prevention, food ingredients high in saturated fat, such as lean meat, are considered risk factors for colon cancer. Diet is thought to have a strong impact on the risk of colorectal cancer, and changes in eating habits can reduce the burden of this cancer by up to 70%. Read again- Mask or Double Mask? Understand Effective Masking Etiquette

Other known epidemiological risk factors for colon cancer are family history, inflammatory bowel disease, smoking, and type 2 diabetes. However, of all the risk factors that increase the risk of colon cancer, diet is one of the environmental and lifestyle factors, and knowing the exact association will only change people’s behavior and eating habits. It may be the easiest to control. Read again- Horoscope on Friday, June 11th today: Gemini is occupied by domestic affairs and SSS should believe in their instincts

“There is epidemiological evidence that there is a strong link between obesity and increased tumor risk,” said Miyeko Mana, assistant professor of life sciences.

“In the gut, stem cells are the cells that are more likely to cause cancer, so what’s the connection? Well, diet nourishes that cycle of obesity and colorectal cancer. . “

A new Arizona State University study, led by Mana and her team, shows in more detail than ever that a high-fat diet can cause molecular cascade events that lead to gut and colon cancer.

Story from the basement

As food breaks down and passes through the intestine, they interact with intestinal stem cells (ISCs) that lie along the inner surface of the intestine. These ISCs reside in a series of regularly folded intestinal valleys called crypts.

The ISC is thought to be the gateway that regulates intestinal tumorigenesis when adapting to a high-fat diet and increasing the risk of cancer. Within the ISC are high-fat sensor molecules that sense and respond to intracellular high-fat diet levels.

“I came across PPAR while following up on the mechanisms that stem cells need to adapt to a high-fat diet,” says Mana. These peroxisome proliferator-activated receptors (or PPARs) trigger cellular programs that increase the risk of cancer, because there are multiple types of PPARs and their role is complex to elucidate. The exact mechanism was unknown.

“There are three families of PPARs: delta, alpha, and gamma. At first I thought that only PPAR delta was involved, but to see if that gene is really involved in the phenotype. , We need to get rid of it, “Mana added.

The mana team was able to investigate and elucidate the role of individual PPAR deltas and alphas using a mouse model that controls intracellular activity. In her team’s study, mice were fed a long-term high-fat or normal diet, and the activity of each PPAR was carefully monitored to study its effect on cancer risk.

In their knockout study, they first deleted the PPAR delta gene.

“But when I removed it from the gut, the phenotype was still observed, so I wondered if another PPAR was making the correction, so I thought about PPAR alpha. Both of them (PPAR). Delta and PPAR alpha) appear to be required for this high-fat diet phenotype within stem cells, “says Mana.

Mana was frustrated by the fact that he quickly realized that developing a potential remedy to offset PPAR would be a much more difficult task.

“If you think of this therapeutically, if you want to include more fat in your diet and reduce your risk of colon cancer, targeting two different factors is more difficult than targeting just one. “Mana added.

Look further downstream

To further elucidate the genetic complexity, Mana then turned his attention to the lower reaches of PPAR.

From their studies, and using new tools in the trade, they were able to slowly reveal details: molecular sequencing from individual cells from different regions of the small intestine and colon, mass spectrometry. Various metabolites for measuring carbon flow to the level of doing, and radioactively labeled isotopes of fuel sources.

Their first big clue came from metabolic analysis. The high-fat diet found in the ISC crypto cells they isolated increased fat metabolism and at the same time reduced sugar breakdown.

“Therefore, we investigated further downstream what these two factors (PPARs) might be targeting.“ This is to import long-chain fatty acids (LCFAs) into mitochondria for use. LCFA is part of a high-fat diet. “

Then, when we conducted a mouse knockout study of Cpt1a, we found that tumor formation could be stopped prematurely. Loss of Cpt1a prevented both ISC dilation and proliferation in the crypts.

“Removing Cpt1a can avoid this high-fat diet phenotype in intestinal stem cells,” says Mana. “That is, at this point you can reduce the risk of tumorigenesis.”

Introducing a new model

From their data, Mana’s team was able to track the development of cancer from diet to tumorigenesis.

First, fat is broken down into free fatty acids. Free fatty acids then stimulate sensors such as PPAR to turn on genes that can break down fatty acids.

The excess free fatty acids are then carried to the mitochondria, where they are oxidized to burn them and generate more energy to supply them to the stem cells, which proliferate, grow and regenerate intestinal tissue. However, as the number of ISCs increases, only random mutations and large numbers of cells are more likely to cause mutations that lead to colon cancer.

“The idea is that this large cell pool stays in the intestine and accumulates mutations, which means that these cells can be sources of mutant cells that lead to transformation and tumor development,” Mana said. Says. “If there are conditions to expand the stem cell pool, we think it is likely.”

The mana group also found that feeding a high-fat diet dramatically accelerated mortality in this model compared to control conditions by accelerating tumorigenesis.

“The levels of these fats we can get from our diet will probably affect stem cells in a fairly straightforward way,” Mana said. “One of the amazing things we found in our research is: That means fatty acids can have such a direct effect. However, these PPARs can be removed, CPT1a can be removed, and the intestines are normal. “

New hope

New evidence from this study hopes that one day their study will be applied to human colon cancer.

“All of these studies have been done on these mouse models so far,” says Mana.

“One of the ideas we started with was to understand the metabolic dependence of tumors that can occur in natural or pharmacological situations, and to make these metabolic programs damage tumors rather than normal tissues. It was targeted. We are advancing a high-fat diet model, but ultimately the goal is to eradicate or prevent human colon-rectal cancer, “Mana concludes. (Ani)