Research identifies ways to protect neurons from negative effect of high-fat diet on MS progression

November 04, 2024
A new study has identified crucial links between dietary choices and the progression of multiple sclerosis. The researchers explored how specific enzymes are responsible for the toxic effect of a palm oil-rich diet on neurons in the central nervous system, which causes a subsequent increase in the severity of MS symptoms.

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 research reported on the toxic effect of a high-fat diet on the severity of MS symptoms. That work explored potential mechanisms in which a diet rich in palm oil may hijack neuronal health.

Using the experimental autoimmune encephalomyelitis model of inflammatory demyelination, researchers at the Advanced Science Research Center at the CUNY Graduate Center’s Neuroscience Initiative and Einstein Professor of Biology and Biochemistry at the CUNY Graduate Center, found diets high in palm oil led to a more severe disease course in mice.

The study’s authors reasoned that inside neuronal cells, palm oil is converted into a toxic substance called C16 ceramide by specific enzymes called ceramide synthase 5 and 6. This ceramide is responsible for inflicting mitochondrial damage, which deprives neurons of the energy they need to counteract inflammation in the brain. They, therefore, asked whether inactivation of these enzymes would confer neuroprotection.

The researchers found that when they genetically deleted the enzymes ceramide synthase 5 and 6 in neurons, they could prevent neurodegeneration in the experimental model of MS.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the 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 an effect 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.

The researchers noted their findings provide a molecular explanation for how to protect neurons from the palm-oil-dependent creation of molecules that harm them. They hope this information can empower patients to make informed dietary decisions that could positively affect the course of the disease, while identifying strategies to counteract the effect of and CerS5 and 6 in a neuron-specific fashion.

The findings were published in the journal Glia.

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