Study IDs 2 enzymes that mediate toxic effects of saturated fats in MS
Enzymes may serve as potential targets for easing neurodegeneration
Two enzymes in brain cells are responsible for mediating the toxic effects of certain fat molecules in multiple sclerosis (MS), a new study in a mouse model of the disease suggests.
According to the researchers, these enzymes may serve as potential targets for easing neurodegeneration in people with MS.
“This new information points to a specific metabolic pathway through which dietary fats can worsen MS symptoms,” Damien Marechal, PhD, coauthor of the study at City University of New York (CUNY), said in a university news story.
The findings build on a growing body of research that indicates a diet with too much fat — especially the saturated fats abundant in fried and processed foods — can have negative impacts on health for those with MS, the researchers noted.
This work “supports previous studies in MS patients on the importance of a healthy diet as [a] modulator of disease course,” the team wrote.
The study, “Neuroprotective effect of neuron-specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis,” was published in Glia.
Seeking ways to stop toxic effects of saturated fats
Diet is known to have profound and complex impacts on human health. While there isn’t much definitive data on the effects of different diets among people with multiple sclerosis, it’s generally recommended that MS patients try to eat a well-balanced diet that provides all necessary nutrients without consuming too much fat or sugar.
Saturated fats in particular, which are known to increase the risk for heart disease, have been suggested to have detrimental effects in MS. But the biological details of how these fats might worsen MS have not been clear.
Now, an international team led by U.S. scientists has shed new light on the toxic effects of saturated fats in mice with experimental autoimmune encephalomyelitis (EAE), a lab-induced disease that’s often used to model MS.
The researchers found that, when the mice were fed a diet high in palm oil — a source of saturated fats that’s present at high levels in many processed and fatty foods — they had more severe disease. This included worse motor symptoms and more damage to nerve fibers in the brain and spinal cord. The animals also had greater levels of fat molecules called ceramides.
Within the brain, a specific fat in palm oil is converted into a toxic molecule called ceramide C16. The conversion of fat into this toxic molecule is mediated by two enzymes, CERS5 and CERS6.
To study whether this toxic ceramide was causing the worsened disease severity in mice fed the diet rich in palm oil, the researchers engineered mice to lack these two enzymes. That meant that fats couldn’t be converted into ceramide C16.
When these engineered mice were fed a high-fat diet, they had markedly less severe symptoms and less nerve fiber damage than was seen in healthy mice fed the diet.
“When both [CERS5 and CERS6] enzymes were deleted in neurons, mice showed a milder EAE course, even when challenged with a high-fat diet enriched in palmitic acid, which serves as precursor for ceramide C16 synthesis,” the researchers wrote. This result “is suggestive of the importance of reducing neuronal-specific generation of C16 ceramides for the severity of the disease,” they added.
We hope this information can empower patients to make informed dietary decisions that could positively impact the course of the disease.
Further experiments indicated that ceramide C16 specifically causes defects in mitochondria in nerve cells. Mitochondria are cellular structures needed to generate energy, and nerve cells are especially sensitive to mitochondrial damage because they need a lot of energy for the busy work of sending electrical signals.
Overall, the researchers said these findings add new evidence supporting the idea that eating a diet high in saturated fats may be detrimental for people with MS, and suggest novel approaches to treating the disease.
“Our research provides a molecular explanation for how to protect neurons from the palm-oil-dependent creation of molecules that harm them,” said Patrizia Casaccia, MD, PhD, a study co-author and professor at CUNY, whose lab had previously reported on the toxic effects a high-fat diet can have on MS symptom severity.
“We hope this information can empower patients to make informed dietary decisions that could positively impact the course of the disease, while identifying strategies to counteract the effect of CerS5 and CerS6 in a neuron-specific fashion,” Casaccia added.
Funding for the research came from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health.
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