Researchers show link between high fat diet, nitric oxide levels and cancer development

It has long been hypothesized that dietary habits may precede and even exacerbate the development of cancer.

Researchers from the Beckman Institute for Advanced Science and Technology have proven that there is a direct link between the amount of fat included in the diet and body levels of nitric oxide, a natural signaling molecule linked to inflammation and the development of cancer.

“We are trying to understand how subtle changes in the tumor microenvironment affect cancer progression at the molecular level. Cancer is a very complicated disease,” said Anuj Yadav, senior research associate and co-lead author of the study.

Yadav explained that cancer is not just about a few tumor cells, but rather the whole microenvironment -; or ecosystem -; of tumor supporting cells.

“Inflammation may play an important role in this environment. Some inflammatory responses come from highly processed, high-calorie, high-fat foods. We wanted to understand the links between foods, inflammation and tumors at the molecular level .had to develop advanced probes to be able to visualize these changes,” he said.

Yadav and his coauthors are aware of the existing research linking increased nitric oxide levels to inflammation, and inflammation to cancer. Proving the link between high-fat diets and nitric oxide levels at the molecular level required the development of a highly sensitive molecular probe capable of deep tissue imaging.

A molecular probe is a group of atoms or molecules used to study the properties of adjacent molecules by measuring the interactions between the probe and the structures of interest. But they are not one size fits all. Each probe must be adapted to the conditions of its experiment.

“Our group specializes in making designer molecules, which allows us to examine molecular features invisible to the naked eye,” said Jefferson Chan, associate professor of chemistry at the University of Illinois at Urbana. -Champaign and principal investigator of the study. “We’re custom-designing these molecules to discover things that weren’t known before.”

The success of the study, published in AEC Core Sciences in March, was largely dependent on the molecular probe designed by the team. Labeled BL660-NO, this probe is the first of its kind to be used in bioluminescence imaging of nitric oxide in cancer.

The researchers used the probe to design a feeding study in mice, comparing the tumorigenicity of mice with breast cancer on a high-fat diet (60% of calories from fat) with mice on a low-fat diet (10% calories from fat) by measuring nitric oxide levels in both groups.

“Due to the high-fat diet, we found an increase in nitric oxide in the tumor microenvironment,” said Michael Lee, a student researcher at the Chan lab and co-lead author of this study. “The implication of this is that the tumor microenvironment is a very complex system, and we really need to understand it to understand how cancer progression works. Many factors can come into play, from diet to exercise – It shouldn’t really be taken into account when we’re considering cancer treatments.”

The authors stressed the importance of proving a direct link between a high-fat diet, nitric oxide levels and the development of cancer. Now that this association is known, new implications exist for the diagnosis and treatment of cancer.

“Without this technology, you wouldn’t see this missing molecular link,” said Chan, who is also a researcher at the Beckman Institute. “Now that we know this is happening, how can we prevent it and how can we improve the situation?”