New research identifies ways to protect neurons from the negative effect of high-fat diet on multiple sclerosis progression

MS is an inflammatory autoimmune disease marked by extensive damage to the insulating myelin sheath that protects nerves throughout the body. Current treatments focus on controlling the immune system's response, but the precise mechanisms contributing to neurodegeneration in MS remain poorly understood. Previous work from the Casaccia lab and others had reported on the toxic effect of high-fat diet on the severity of MS symptoms. In their study, researchers explored potential mechanisms by which a diet rich in palm oil may hijack neuronal health.

Neuroprotection From Palm Oil-Induced Toxicity

Using the experimental autoimmune encephalomyelitis (EAE) model of inflammatory demyelination, the research team found that diets high in palm oil led to a more severe disease course in mice.

"We reasoned that inside neuronal cells, palm oil is converted into a toxic substance called C16 ceramide by specific enzymes called CerS5 and CerS6," said principal investigator Casaccia. "This ceramide is responsible for inflicting mitochondrial damage, which deprives neurons of the energy they need to counteract inflammation in the brain. We therefore asked whether inactivation of these enzymes would confer neuroprotection."

The researchers found that when they genetically deleted the enzymes CerS6 and CerS5 in neurons they could prevent neurodegeneration in the experimental model of MS.

"This held true even when mice were fed a diet rich in palmitic acid," said the paper's co-first author Damien Marechal, a research associate with the Casaccia Lab. "This new information points to a specific metabolic pathway through which dietary fats can worsen MS symptoms."

Significance for MS Patients and Clinicians

The paper's findings have significant implications for individuals diagnosed with MS as well as for clinicians treating patients and neuroscientists researching the disease. The work reinforces that lifestyle choices, such as diet, can have a profound impact on the course of the disease. The study's results build on previous concepts about careful dietary choices in managing the symptoms of MS. The findings also identify potential molecules that could help slow diet-induced symptom severity.

"Our research provides a molecular explanation for how to protect neurons from the palm-oil-dependent creation of molecules that harm them," said Casaccia. "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."

The research was funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH).