High Fat Diet Activates Immune System Leading To Intestinal Tumors

A high fat diet triggers immune reaction which causes inflammation leading to intestinal cancer. The new study, from the Perelman School of Medicine at the University of Pennsylvania, Case Western Reserve University, the Pacific Northwest Research Institute (PNRI), and others, was demonstrated in a mouse model and that too among animals that are not obese.

Epidemiological and clinical evidence have linked obesity with inflammation and increased risk of cancer. Up to now, however, the molecular mechanisms linking these three conditions have been elusive. The interdisciplinary team published their findings in Molecular Cancer Research.

“We found that specific types of high-fat diets – based on corn or coconut oils like those found in certain salad dressings and ice cream -- are associated with increased tumor formation in a mouse model of intestinal cancer,” said co-senior author John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine at Penn. “This model is particularly interesting because it resembles human familial adenomatous polyposis, a condition that carries an 80% risk of developing colorectal cancer in individuals with mutations in a tumor suppressor gene called Apc.”

Mice who were fed corn or coconut fats showed increased tumor formation, those fed diets with olive oil as a source of fat did not develop intestinal polyps, despite being obese.

“This observation led us to our first important conclusion that diet, but not necessarily obesity, can promote intestinal cancer,” said co-author Edimara Reis, PhD, a research associate in the Department of Pathology and Laboratory Medicine. The FDA decided to give the food industry three years to phase out partially hydrogenated oils, the main source of trans fat in some foods based on corn oil and other types of fat in September 2015.

The team concluded that a high-fat diet (rather than metabolic status) and the chemical composition of the diet are the most important factors for determining cancer risk, using the mouse model, which was developed by co-senior author Joseph Nadeau from PNRI and first author Stephanie Doerner from Case Western.

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"Our results clearly show that eating a high-fat diet is sufficient to increase cancer risk, regardless of obesity,” said co-senior author Nadeau.

The corn and coconut based high fat diets triggered inflammation by activating the immune system and led to tumor formation. In mice, the inflammation and intestinal tumors in the mice were triggered very soon , in a matter of three days, after being fed these high-fat diets.

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The corn and coconut based diets activated the complement system, an arm of the innate immune system, but not the olive oil-based diet.

Complement is an evolutionarily conserved network of proteins that regulate the part of immune responses which destroy foreign invaders. From primitive sponges to humans, the system is a rapid defense mechanism. Complement also has inflammatory functions, and the Lambris lab has been investigating C5aR (the C5a receptor) for more than two decades. In the current study, in mice fed corn and coconut based high fat diets, C5a, a related pro-inflammatory molecule, increased in the intestine and systemically.

“When mice were given a drug to reduce the activity of C5aR, it prevented the development of intestinal tumorigenesis in mice fed corn- and coconut HFDs, indicating that anti-complement therapy could act as an adjuvant with cancer treatments,” Lambris said. The team also surmises that a diet change and complement inhibitors could potentially be beneficial to people with the apc mutation to prevent carcinogenesis.

Source-Medindia