The negative effect of high-fat diet on multiple sclerosis progression

Western high-fat diet can cause chronic pain, according to UT Health San Antonio-led team

Recent research published in the journal *Glia* has uncovered important connections between dietary choices and the progression of multiple sclerosis (MS). The study, led by Patrizia Casaccia, the founding director of the Advanced Science Research Center at the CUNY Graduate Center’s Neuroscience Initiative and an Einstein Professor of Biology and Biochemistry at the same institution, investigated the role of enzymes known as ceramide synthase 5 and 6. These enzymes are linked to the harmful effects of a diet high in palm oil on neurons in the central nervous system, which may lead to an increase in the severity of MS symptoms.

Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by significant damage to the myelin sheath, which protects nerves throughout the body. Current treatments aim to control the immune system’s response, but the exact mechanisms leading to neurodegeneration in MS are still not well understood. Previous research from the Casaccia lab and others has indicated that a high-fat diet can exacerbate the severity of MS symptoms. In their study, researchers investigated potential mechanisms by which a diet high in palm oil may negatively affect neuronal health.

Neuroprotection From Palm Oil-Induced Toxicity

In the experimental autoimmune encephalomyelitis (EAE) model of inflammatory demyelination, researchers discovered that mice with diets high in palm oil had a more severe disease course.

“We hypothesized that within neuronal cells, palm oil is transformed into a toxic substance known as C16 ceramide by specific enzymes called CerS5 and CerS6,” explained principal investigator Casaccia. “This ceramide causes damage to mitochondria, depriving neurons of the energy they require to combat inflammation in the brain. Consequently, we investigated whether inactivating these enzymes could provide neuroprotection.”

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

“This was true even when mice were given a diet high in palmitic acid,” said Damien Marechal, a research associate with the Casaccia Lab and co-first author of the paper. “This new information highlights a specific metabolic pathway that shows how dietary fats can exacerbate MS symptoms.”

Significance for MS Patients and Clinicians

The paper’s findings have significant implications for individuals diagnosed with MS, clinicians treating patients, and neuroscientists researching the disease. The work reinforces that lifestyle choices, such as diet, can profoundly impact the course of the disease. The study’s results build on previous concepts about careful dietary decisions 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.”