Sugar Found in Red Meat Causes Chronic Inflammation in Human-Like Mouse Model

Chronic inflammation in humans, which has been linked to tumor formation as well as development of other syndromes such as atherosclerosis and type II diabetes, may be a response to red meat in the diet that contains the sugar N-Glycolylneuraminic acid (Neu5Gc).

Humans differ from other mammals by being unable to synthesize Neu5Gc, as the human CMAH gene has been irreversibly mutated and produces an inactive form of the enzyme CMP-N-acetylneuraminic acid hydroxylase, which is the enzyme responsible for synthesizing CMP-Neu5Gc from CMP-N-acetylneuraminic (CMP-Neu5Ac) acid. Even though Neu5Gc cannot be produced by humans, it has been found in human cancers and fetal samples, which suggests that molecules of Neu5Gc enter human pathways through external sources, such as diet. Some researchers have suggested that eating red meat could lead to inflammation if the body’s immune system constantly generates antibodies against consumed animal Neu5Gc, a foreign molecule.

To study the relationship between red meat consumption and tumor development, investigators at the University of California, San Diego (USA) genetically engineered a mouse model to mimic the human condition by lacking Neu5Gc.

The investigators first evaluated the Neu5Gc content of various foods and showed that red meats were particularly rich in orally bioavailable Neu5Gc. They then fed this form of Neu5Gc to the human-like Neu5Gc-deficient mice. Results published in the December 29, 2014, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) revealed that when such mice were challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Long-term exposure to this combination resulted in a significantly higher incidence of carcinomas (five-fold increase) and an association with Neu5Gc accumulation in the tumors.

“Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups,” said senior investigator Dr. Ajit Varki, professor of medicine and cellular and molecular medicine at the University of California, San Diego. “This is the first time we have directly shown that mimicking the exact situation in humans — feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies — increases spontaneous cancers in mice.”

“The final proof in humans will be much harder to come by,” said Dr. Varki. “But on a more general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type II diabetes. Of course, moderate amounts of red meat can be a source of good nutrition for young people. We hope that our work will eventually lead the way to practical solutions for this catch-22.”

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University of California, San Diego