Altered adipokine levels are associated with dimethyl fumarate treatment in multiple sclerosis patients

Moogeh Baharnoori; Ryan Wilson; Shrishti Saxena; Cindy T Gonzalez; Marinos G Sotiropoulos; Kiandokht Keyhanian; Brian C Healy; Tanuja Chitnis

doi:10.1016/j.msard.2021.103311

Altered adipokine levels are associated with dimethyl fumarate treatment in multiple sclerosis patients

Mult Scler Relat Disord. 2021 Nov:56:103311. doi: 10.1016/j.msard.2021.103311. Epub 2021 Oct 4.

Authors

Moogeh Baharnoori¹, Ryan Wilson², Shrishti Saxena³, Cindy T Gonzalez³, Marinos G Sotiropoulos¹, Kiandokht Keyhanian¹, Brian C Healy¹, Tanuja Chitnis⁴

Affiliations

¹ Brigham 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.
² Brigham Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Boston, MA, US; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, US; Harvard College, Cambridge, MA, US.
³ Brigham Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Boston, MA, US; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, US.
⁴ Brigham 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. Electronic address: tchitnis@rics.bwh.harvard.edu.

PMID: 34655958
DOI: 10.1016/j.msard.2021.103311

Abstract

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.

Keywords: Multiple sclerosis; adipokine; biomarker; dimethyl fumarate.

Publication types

Observational Study

MeSH terms

Adipokines / blood*
Adiponectin / blood
Cohort Studies
Cross-Sectional Studies
Dimethyl Fumarate* / therapeutic use
Fatty Acid-Binding Proteins / blood
Female
Humans
Immunosuppressive Agents
Male
Multiple Sclerosis* / blood
Multiple Sclerosis* / drug therapy

Substances

Adipokines
Adiponectin
FABP4 protein, human
Fatty Acid-Binding Proteins
Immunosuppressive Agents
Dimethyl Fumarate