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. 2022 Dec 15:15:1077381.
doi: 10.3389/fnmol.2022.1077381. eCollection 2022.

Fingolimod treatment modulates PPARγ and CD36 gene expression in women with multiple sclerosis

Véronique Ferret-Sena  1 , Carlos Capela  2 , Ana Macedo  3   4 , António Vasco Salgado  5 , Bruno Derudas  6 , Bart Staels  6 , Armando Sena  1   2
Affiliations

Fingolimod treatment modulates PPARγ and CD36 gene expression in women with multiple sclerosis

Véronique Ferret-Sena et al. Front Mol Neurosci. .

Abstract

Fingolimod is an oral immunomodulatory drug used in the treatment of multiple sclerosis (MS) that may change lipid metabolism. Peroxisome proliferator-activated receptors (PPAR) are transcription factors that regulate lipoprotein metabolism and immune functions and have been implicated in the pathophysiology of MS. CD36 is a scavenger receptor whose transcription is PPAR regulated. The objective of this study was to evaluate whether fingolimod treatment modifies PPAR and CD36 gene expression as part of its action mechanisms. Serum lipoprotein profiles and PPAR and CD36 gene expression levels in peripheral leukocytes were analysed in 17 female MS patients before and at 6 and 12 months after fingolimod treatment initiation. Clinical data during the follow-up period of treatment were obtained. We found that fingolimod treatment increased HDL-Cholesterol and Apolipoprotein E levels and leukocyte PPARγ and CD36 gene expression. No correlations were found between lipid levels and variations in PPARγ and CD36 gene expression. PPARγ and CD36 variations were significantly correlated during therapy and in patients free of relapse and stable disease. Our results suggest that PPARγ and CD36-mediated processes may contribute to the mechanisms of action of fingolimod in MS. Further studies are required to explore the relation of the PPARγ/CD36 pathway to the clinical efficacy of the drug and its involvement in the pathogenesis of the disease.

Keywords: cluster of differentiation 36 (CD36); fingolimod; lipoproteins; multiple sclerosis; peroxisome proliferator-activated receptors (PPAR).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PPARα (A), PPARβ/δ (B), PPARγ (C), and CD36 (D) leukocyte gene expressions at baseline, and at 6 and 12 months of treatment with Fingolimod. Value of ps obtained through nonparametric Wilcoxon test are presented.
Figure 2
Figure 2
Spearman correlation between PPARγ fold variation and CD36 fold variation for patients with: No relapses during the 12-months follow-up (A) and No evidence of disease activity (NEDA-3) (B).
See this image and copyright information in PMC

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