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Altered adipokine levels are associated with dimethyl fumarate treatment in multiple sclerosis patients
Moogeh Baharnoori1, Ryan Wilson2, Shrishti Saxena3
1Brigham Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Boston, MA, US; Harvard Medical School, Boston, MA, US; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, US.
Background:
Obesity is linked to increased risk of multiple sclerosis (MS) and worsening disease severity. Recent experimental and clinical data indicates that adipokines are involved in regulating immune response and serve as cross talk between immune and neural system. Dimethyl fumarate (DMF) is an oral MS medication with unknown mechanism of action. It upregulates the nuclear factor E2-related factor 2 (Nrf2) pathway, a pathway for adipocyte differentiation. To determine a possible relationship between treatment with dimethyl fumarate, serum adipokine profiles and treatment response in patients with MS, we conducted an observational cohort study and measured serum adipokine and Vitamin D levels before and after treatment with DMF and examined their association with treatment response.
Methods:
We identified patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study who were treated with dimethyl fumarate and had available serum samples. Longitudinal pre-treatment and on-treatment samples were available in 23 patients. Cross-sectional on-treatment samples were available in 91 patients, who were classified into DMF responders and non-responders based on radiologic and clinical relapse activity or disability progression. We measured serum leptin, adiponectin, resistin, ghrelin, fatty acid binding protein-4 (FABP-4) and-5 (FABP-5), vitamins D2 and D3. Statistical analysis was performed with paired t-tests, Wilcoxon signed-rank and Mann-Whitney U tests.
Results:
After treatment with DMF, serum adiponectin levels significantly increased, whereas FABP-4 levels significantly decreased compared to baseline levels, without a statistically significant change in the patients' BMI. Ghrelin levels were insignificantly lower post-treatment. FABP-4 levels were significantly higher in DMF responders compared to non-responders. This effect was sex-specific, with higher FABP4 levels associated with treatment response in males, but not females.
Conclusion:
DMF treatment is associated with significant changes in serum adipokine levels, primarily adiponectin and FABP-4. Sex may affect the association between FABP-4 and treatment response.
Insights
Dimethyl fumarate (DMF) treatment for multiple sclerosis (MS) alters adipokine levels, with increased adiponectin and decreased FABP-4. FABP-4 levels predict treatment response, particularly in males.
Area of Science:
- Neuroimmunology
- Metabolic disease research
- Pharmacology
Background:
- Obesity is a risk factor for multiple sclerosis (MS) and disease severity.
- Adipokines mediate immune and neural system crosstalk.
- Dimethyl fumarate (DMF) is an oral MS medication with an unclear mechanism of action, potentially linked to the Nrf2 pathway involved in adipocyte differentiation.
Purpose of the Study:
- To investigate the relationship between dimethyl fumarate (DMF) treatment, serum adipokine profiles, and treatment response in MS patients.
- To measure changes in serum adipokine and Vitamin D levels before and after DMF treatment.
Main Methods:
- Observational cohort study of MS patients treated with DMF.
- Analysis of longitudinal and cross-sectional serum samples from 23 and 91 patients, respectively.
- Measurement of serum adipokines (leptin, adiponectin, resistin, ghrelin, FABP-4, FABP-5) and Vitamin D levels.
- Classification of patients into DMF responders and non-responders based on clinical and radiologic outcomes.
Main Results:
- DMF treatment led to significant increases in serum adiponectin and decreases in FABP-4 levels, independent of BMI changes.
- FABP-4 levels were significantly higher in DMF responders compared to non-responders.
- The association between higher FABP-4 levels and treatment response was specific to males.
Conclusions:
- Dimethyl fumarate (DMF) treatment significantly alters serum adipokine profiles, notably increasing adiponectin and decreasing FABP-4.
- Serum FABP-4 levels may serve as a predictive biomarker for DMF treatment response in MS patients, with a potential sex-specific effect.
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