Study of the deterioration of multiple sclerosis related to excess body fat and its impact on immune cells

One study indicates that the link between fat molecules called ceramides and the worsening of the disease in obese or obese people with multiple sclerosis (MS) suggests that ceramides stimulate the growth of immune cells called monocytes, which which accelerates the progression of the disease. .

These findings also reinforce the likelihood that lifestyle factors, such as diet and weight, may act as modifiers of the disease, his researchers said.

The study, "Body mass index in multiple sclerosis modulates the methylation of DNA-induced ceramides and the course of the disease, "Was published in the newspaper EBioMedicine.

The high body mass index (BMI) has been associated with the risk of developing MS, but for reasons that are unclear. One idea is that weight-induced differences in lipids (fat molecules) in the blood, because they are involved in several cellular signaling processes, can affect MS and its evolution in people with high BMI.

To test this hypothesis, a team led by researchers from the Graduate Center's Advanced Scientific Research Center (ASRC) and Mount Sinai School of Medicine Icahn analyzed 54 patients with relapsing-remitting MS (MS), aged 18 years. at 60 years old. and with a normal or high BMI (27 people in each group). The participants were followed for two years.

BMI is a measure of body fat based on height and weight. A normal BMI is defined as between 18.5 and 24.9, while a person is considered overweight with a BMI of 25 to 29.9 and the obese is 30 or more.

The researchers took blood samples and looked for differences between the groups in terms of immune cells and blood lipid profiles. They then validated their findings in a separate group of 91 RRMS patients.

Patients with high BMI tended to have more monocytes than those with normal BMI. Monocytes can travel through the blood to tissues where they develop into macrophages, immune cells with varied functions and better known for "eating" invading bacteria. Monocytes can also travel to the brain and damage nerve fibers.

Overweight and obese patients also had significantly higher ceramide levels compared to normal weight patients, and the researchers wondered if there was a link between the two.

Through a series of experiments on cells, they discovered that ceramides caused epigenetic changes in monocytes; that is, they alter how their genomes are "read", so that they alter the activity of the genes. Specifically, ceramide-treated cells exhibited a type of epigenetic change called methylation – which usually disables genes – in genes that normally help to prevent cells from dividing.

Conceptually, these genetic changes serve to release monocytes, causing them to grow (proliferate) more than they could otherwise.

The researchers also found greater methylation on the genome of monocytes in high BMI patients than in those with low BMI patients. MRI (Magnetic Resonance Imaging) scans the follow up.

Finally, the researchers tested a mouse model of multiple sclerosis, giving one group of mice a standard diet and another a diet high in fat. Mice fed the high-fat diet had greater disease severity, more brain damage and more monocytes, confirming the results seen in MS patients.

"This study gives us an indispensable view of the environmental influences that can affect and alter the behavior of cells in the body of an individual," said Kamilah Castro, the first author of the study, in a press release. "Our results suggest that increasing saturated fat levels as a result of eating habits is one of the likely causes of epigenetic changes that advance MS, giving us a starting point for a potential intervention. "

According to the team, the results support the concept of nutrition-epigenomics, that is, the ability of foods to alter how genetic information is interpreted by each cell, and suggest that "weight management and food intervention "could affect the prognosis of MS.

One of the limitations was the small size of the study, noted his researchers. "We consider our results to be … very exciting and mechanistic, but we recognize that potential consideration of ceramide levels as biomarkers of disease progression in MS would require validation … using larger cohorts with a plan. longitudinal and / or transversal ", they concluded. "It will also be important to evaluate the effectiveness of dietary intervention (with emphasis on reducing specific classes of saturated fat), as a potential modulator of plasma levels of ceramide and, possibly, the course of the disease in patients with MS. "

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