The body mass index can play an important role in the progression of multiple sclerosis

NEW YORK, April 11, 2019 – An article recently published in the Lancet newspaper EBioMedicine identifies a link between high blood lipid levels and worsening of the disease in overweight or obese multiple sclerosis (MS) patients.

The longitudinal survey, conducted by researchers at New York University's Advanced Neuroscience Research Center, in collaboration with clinicians from Mount Sinai's Icahn School of Medicine, was followed by two researchers. years. The researchers found that overweight or obese individuals had higher levels of blood lipids called ceramides, which placed markers on monocyte DNA, which made them proliferate. Monocytes are blood cells that can travel to the brain and damage nerve fibers. Two years after diagnosis, study participants with elevated ceramide and monocyte levels also had a greater loss of motor function and brain damage.

"Our study identifies important correlations between ceramide levels, body mass index and disease progression in patients with multiple sclerosis," said Patrizia Casaccia, director of the Neuroscience Initiative CURC, a professor at the Graduate Center. "We found that people who are overweight and obese with MS have higher ceramide levels than people with the disease who are not overweight and also overweight or obese but under healthy conditions. is important because we have already identified cerebrospinal fluid surrounding the brains of multiple sclerosis patients, and we attributed their increased abundance to the efforts of the body to recycle damaged myelin.In this study, we also detected higher ceramide levels in the blood we did in patients with normal body mass index, suggesting that overabundant lipids may be derived not only from damaged brain cells, but also from Excessive dietary intake of saturated fats. "

Methodology

Two cohorts of patients – a primary and a validation group – were recruited at the Multiple Sclerosis Center Corinne Goldsmith Dickinson in Mount Sinai and at the National Institutes of Health to participate in the study. For the first group, 54 patients with treatment-naive multiple sclerosis aged between 18 and 60 years with a high or normal body mass index (BMI) were evaluated with the aid of a cerebral MRI. to identify the signs of cerebral involvement; a clinical assessment to determine weight, disability and other vital information; and blood tests to analyze the types of lipids and white blood cells in circulation. An independent validation group of 91 MS patients from the National Institute of Health with the same characteristics and additional control cohorts of healthy individuals in the same IMC range were evaluated in a similar way.

The researchers found that patients with multiple sclerosis with a high BMI had higher ceramide levels and more monocytes in circulation than those seen in healthy people with the same BMI. Patients with high BMI SM exhibited an aggravation of disability and more brain damage to MRI compared to their normal BMI counterparts. The researchers then discovered that ceramides could penetrate inside immune cells called monocytes and alter how these cells read genetic information encoded in DNA. These epigenetic modifications have also been observed in circulating monocytes in the blood of MS patients with high BMI.

Importance

The detection of ceramides in the nucleus of blood cells and the ability of these lipids to induce epigenetic changes suggest that saturated fatty acids can have lasting functional effects, which, over time, orients the evolution of the MS disease towards an aggravation of disability. In short, poor eating habits can have negative consequences in healthy subjects, but they have an even more pronounced deleterious effect in MS patients because degrading myelin can accumulate and increase the rate further. of ceramides.

"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 newspaper's first author and graduate student of Professor Casaccia's laboratory. "Our findings suggest that increasing saturated fat levels due to eating habits is one of the likely causes of epigenetic changes that advance MS, which gives us the starting point for A potential intervention. "

The researchers' conclusions support the concept of epigenomic nutrient (ability of food to alter how genomic information is interpreted by each cell) and the idea that lifestyle factors, such as diet food and weight, can act as modifiers of the disease. Additional studies on larger cohorts are needed to validate current results. Further investigation is also needed to determine whether specific dietary interventions and weight management could be helpful in helping MS patients manage and slow the progression of their disease and better respond to DMARDs.

"This translational study is exciting from a clinical point of view because it highlights a potentially important mechanism that could help us explain our clinical observations regarding obesity and prognosis of MS," he said. Ilana Katz Sand, Associate Medical Director of the Corinne Goldsmith Dickinson Center for MS at Mount Sinai. "We look forward to continuing to work on this important topic in future clinical studies to evaluate the impact of weight management and dietary interventions on MS."

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