The physical state of obesity, rather than the over-consumption of foods that lead to becoming obese, causes changes in the colon that could lead to colorectal cancer, according to a new study.

Writing in the journal Cell Metabolism, researchers suggest that calorie-control and exercise are not only key to a healthy lifestyle, but a strategy to lower the risk of colon cancer, which is the the second leading cause of cancer-related deaths in the US.

For the study, which sought to clarify the link between obesity and cancer predisposition, researchers from the National Institutes of Health (NIH) gave two groups of mice a diet that contained 60 percent lard. One of the groups was given a human version of a gene called NAG-1 which has been shown to protect against colon cancer in other rodent studies. The other group lacked the NAG-1 gene.

Mice without NAG-1 became obese after eating a lard-rich diet, while mice with NAG-1 did not gain weight from the high-fat diet.

Additionally, the researchers observed something peculiar in the obese mice.

"The obese mice exhibited molecular signals in their gut that led to the progression of cancer, but the NAG-1 mice didn't have those same indicators," said study leader Thomas Eling,a scientist at the National Institute of Environmental Health Sciences (NIEHS), which is part of NIH.

Eling and his collaborators, including NIH scientist Paul Wade, searched for molecular clues in the mices' cells, particularly in a group of proteins called histones.

"Histones package and organize DNA in a cell's nucleus, and sometimes undergo a process known as acetylation, in which chemical tags bind to their surface," according to a NIHES statement. "The pattern of acetylation varies depending on the chemical processes taking place in the cell."

Acetylation of proteins in the two groups of mice were drastically different, the researchers report. The obese mice exhibited patterns of acetylation resembling colorectal cancer. The excess weight carried by the obese mice also seemed to activate more genes typically associated with colorectal cancer progression, which suggests the mice are predisposed to colon cancer, the researchers said.

"Any preexisting colon lesions in these animals are more likely to evolve rapidly into malignant tumors," Wade said. "The same thing may happen in humans."

"Once we identify the signaling pathways and understand how the signal is transduced, we may be able to design ways to treat colorectal cancer in obese patients," he added.