Obesity, altered lipid (fat) levels, and elevated leptin — an hormone produced by fat cells — may contribute to neuroinflammation, and worse disease severity in people with relapsing-remitting multiple sclerosis (RRMS), research has found.
A study with the findings, titled “Obesity worsens central inflammation and disability in multiple sclerosis,” was published in Multiple Sclerosis Journal.
Prior studies revealed a link between metabolic unbalance, inflammation, and neurodegeneration in multiple sclerosis (MS). Obesity during childhood and adolescence is a known risk factor for MS, and alterations in the fat, or lipid, metabolism have been associated with a worse disease course in patients.
Researchers at the unit of neurology and neurorehabilitation at IRCCS Neuromed, in Italy, were interested in better understanding the relationship between lipid metabolism and MS because, they said, “interventions aimed at lowering abnormal serum lipid levels could reduce the accumulation of disability.”
To that end, they examined 140 RRMS patients to assess whether an elevated body mass index (BMI; a reflection of body fat mass), and an increase in lipids in the blood at the time of diagnosis, correlated with inflammation of the central nervous system (CNS; brain and spinal cord) and MS severity.
Among the participants, 83 had a normal weight, 33 were considered overweight, and 24 filled the criteria for obese.
Neuroinflammation was assessed by measuring multiple inflammatory molecules in patient samples of cerebrospinal fluid (CSF), a body fluid running through the brain and spinal cord. The CSF was collected by spinal tap.
The investigators then analyzed the lipids concentration in blood (serum), including triglycerides, total cholesterol, and high-density lipoprotein cholesterol (HDL), known as “good” chlolesterol.
The data revealed that, at the time of MS diagnosis, obese patients had a greater risk of disability, as measured by the Expanded Disability Status Scale (EDSS), a commonly used measure of MS severity.
Moreover, obesity was accompanied by higher levels of interleukin-6 (IL-6) and leptin, two well-known promoters of inflammation. Leptin is an hormone, released by fat cells in adipose tissue (a storage organ), that conveys signals to the brain. Leptin also is known to support pro-inflammatory responses against the CNS.
Unlike IL-6 and leptin, the CSF of obese patients tended to have less interleukin-13 (IL-13), an anti-inflammatory factor.
In contrast, more triglycerides and a higher ratio of total to HDL cholesterol — known as “bad” cholesterol — were associated with higher IL-6 levels in the CSF, the researchers said. This supports the relationship between the amount of lipids in the blood and neuroinflammation.
“This study confirms that obesity is associated with greater symptomatic severity of relapsing-remitting multiple sclerosis. In particular, the analysis of cerebrospinal fluid has highlighted the role of leptin produced by fat cells,” Mario Stampanoni Bassi, MD, neurologist at Neuromed and lead author of the study, said in a press release.
The results “suggest that excessive body weight, or altered lipid profile, are associated to increased central inflammation causing a worse clinical expression of the disease,” Stampanoni said.
The team said these findings “could provide new therapeutic opportunities aimed at limiting the negative impact of altered lipid metabolism on inflammatory response in MS, representing useful adjunctive strategies to modify the course of this potentially devastating disease.”
The study’s senior leader, Diego Centonze, MD, PhD, emphasized approaches focused on diet and exercise.
“Specific strategies, such as diet or increased physical activity, may therefore pave the way to the possibility of improving the condition of patients with multiple sclerosis, contrasting the increase of disability over time,” said Centonze, professor at University of Rome Tor Vergata and head of the neurology unit at Neuromed.