How does a high-fat diet raise colorectal cancer risk?

Image result for How does a high-fat diet raise colorectal cancer risk?A new study suggests a molecular explanation for the link between a high-fat diet and colorectal cancer.
While the evidence of a link between an unhealthful diet and colorectal cancer is robust, the underlying mechanisms for this association have been unclear. A new study, however, may have uncovered an explanation.

Researchers from the Cleveland Clinic in Ohio have identified a cellular signaling pathway, called JAK2-STAT3, that drives the growth of cancer stem cells in the colon in response to a high-fat diet.

What is more, the researchers found that blocking the JAK2-STAT3 pathway in mice fed a high-fat diet halted the growth of these stem cells, a finding that might fuel the development of new drugs to treat colorectal cancer.

Study co-author Dr. Matthew Kalady, co-director of the Comprehensive Colorectal Cancer Program at the Cleveland Clinic, and colleagues recently reported their findings in the journal Stem Cell Reports.

After skin cancer, colorectal cancer – a cancer that begins in the colon or rectum – is the third most commonly diagnosed cancer in the United States.

The American Cancer Society estimate that there will be 95,520 new cases of colon cancerdiagnosed in the U.S. this year, as well as 39,910 new cases of rectal cancer.

In recent years, a wealth of studies have suggested that a high-fat diet is a risk factor for colorectal cancer. However, the precise mechanisms behind this association have been ambiguous.

With the hope of shedding light on such mechanisms, Dr. Kalady and colleagues investigated how a high-fat diet influences JAK2-STAT3, a cellular signaling pathway known to promote tumorgrowth.

Findings may fuel new treatments

To reach their findings, the researchers used microrarray analysis to assess primary and metastasized tumors in mouse models of colorectal cancer.

When the mice were fed a high-fat diet, the growth of cancer stem cells in the colon increased. Studies have indicated that cancer stem cells are a key driver in the growth and metastasis of tumors.

On further investigation, the team found that blocking the JAK2-STAT3 cellular signaling pathway in the rodents reversed the increase in cancer stem cell growth triggered by a high-fat diet.

When analyzing the effects of a high-fat diet in colorectal cancer mouse models that were obesity-resistant, the researchers were able to replicate their findings.

Dr. Kalady says that this study is the first to demonstrate how a specific molecular pathway might mediate the link between a high-fat diet and colorectal cancer, a discovery that could yield new treatments for the disease.

We can now build upon this knowledge to develop new treatments aimed at blocking this pathway and reducing the negative impact of a high-fat diet on colon cancer risk.”

Dr. Matthew Kalady

“These findings also provide a new way in which cancer stem cells are regulated and provide insight into how environmental influences, such as diet, can alter cancer stem cell populations in advanced cancers,” adds study co-author Justin D. Lathia, Ph.D., of the Lerner Research Institute at Cleveland Clinic.

[“Source-medicalnewstoday”]

Gene Variant May Drive Hunger For High-Fat Foods

PARIS, FRANCE:  People with a variant of a particular gene prefer high-fat food compared to people without it, said a study Tuesday, suggesting our dietary preferences may be at last partly pre-coded.

Unexpectedly, the same individuals had a reduced taste for sugar, according to a study in the journal Nature Communications.

“Our work shows that even if you tightly control the appearance and taste of food, our brains can detect the nutrient content,” said paper co-author Sadaf Farooqi of the University of Cambridge, whose researchers conducted the study.

Farooqi and a team tested the food preferences of 14 obese individuals with rare variations in the MC4R gene, and compared them to lean people and other obese people without the mutation.

The participants were given an all-you-can-eat buffet of chicken korma, a type of curry.

There were three dishes, differing only in their fat contribution to total calorie content — either 20 percent, 40 percent or 60 percent. The tasters did not know of the difference, and the dishes were made to look the same.

“The researchers found that, although there was no overall difference in the amount of food eaten between the groups, individuals with defective MC4R ate almost double the amount of high fat korma than lean individuals (95 percent more),” the university said in a statement.

They also ate 65 percent more of the high-fat korma than other obese individuals without the genetic quirk.In a second part of the study, the participants were given “Eton mess”, a dessert made of strawberries, whipped cream and pieces of meringue.

There were again three visually indistinguishable options — sugar comprising eight percent, 26 percent or 54 percent of total calories.

Individuals with the gene variant liked the high-sugar desserts less than the others, and ate “significantly less” of all three types.

“One in 100 obese people have a defect in the MC4R gene which makes them more likely to put on weight,” said the statement.

“For these individuals, the fact that the MC4R pathway is not working may led them to preferring high-fat foods without realising it.”

source”cnbc”