How Fat-Derived Molecules Could Shape Multiple Sclerosis Treatment
Multiple sclerosis (MS) is a complex immune-mediated disease where the immune system mistakenly attacks the central nervous system (CNS), leading to inflammation, demyelination, and neurodegeneration. While genetics and environmental triggers are well-known players, researchers are increasingly uncovering another piece of the puzzle: metabolism and fat-derived signaling molecules called adipocytokines.
A new study published in the International Journal of Molecular Sciences (Adamczyk et al., 2025) sheds light on how adipocytokines—namely adiponectin, visfatin, and resistin—behave in patients with relapsing–remitting MS (RRMS) receiving two commonly used second-line therapies: fingolimod and natalizumab.
The findings not only strengthen the link between metabolism and neuroinflammation but also suggest that adipocytokines might serve as biomarkers to monitor treatment response.
Adipocytokines: Messengers from Fat to Brain
Adipose tissue is not just a storage depot for energy—it’s an active endocrine organ. It releases adipocytokines that influence metabolism, immunity, and inflammation.
Adiponectin is generally anti-inflammatory and neuroprotective, enhancing regulatory T-cell function and dampening harmful cytokines.
Visfatin (also known as NAMPT) promotes inflammation and immune cell activation, but also supports cellular energy processes.
Resistin contributes to inflammation (via TNF-α, IL-6, IL-1β) but also has protective roles against oxidative stress.
Previous studies showed that MS patients often display higher resistin and visfatin but lower adiponectin compared to healthy people. This imbalance might fuel chronic inflammation and disability progression.
The Study: Comparing Treatments
The researchers studied 49 RRMS patients (30 on fingolimod, 19 on natalizumab) and 38 healthy controls. They measured serum levels of visfatin, adiponectin, and resistin, and analyzed links with disease duration, treatment time, and body mass index (BMI).
Key findings:
Adiponectin rose significantly in natalizumab-treated patients compared to both fingolimod users and healthy controls.
This suggests natalizumab may boost anti-inflammatory signaling.
In fingolimod-treated patients, visfatin increased with longer treatment duration (>18 months).
Visfatin correlated negatively with BMI, while resistin correlated positively with BMI.
No differences were observed in adipocytokine levels between men and women, or in relation to MRI lesion counts and relapse rates.
What Do These Results Mean?
1. Fingolimod’s Complex Metabolic Effects
Fingolimod, which traps lymphocytes in lymph nodes by modulating sphingosine-1-phosphate receptors, may also influence adipokine metabolism. The increase in visfatin with longer therapy could reflect adaptive metabolic responses—or a drug-specific effect on inflammation pathways. The BMI correlations suggest that patient weight and metabolism might modulate drug effects.
2. Natalizumab and Protective Adiponectin
Natalizumab, a monoclonal antibody that prevents immune cells from entering the CNS, was linked with strikingly higher adiponectin levels. Since adiponectin dampens inflammation and protects neurons, its rise may be part of natalizumab’s therapeutic mechanism. This opens exciting questions about whether adiponectin is a mediator—or simply a biomarker—of treatment success.
3. Adipocytokines as Biomarkers
Because adiponectin, visfatin, and resistin reflect both immune and metabolic states, they could serve as biological readouts of treatment response or disease progression. For example:
A rising adiponectin under natalizumab could indicate favorable immune regulation.
Elevated visfatin or resistin may point to ongoing inflammation or metabolic stress.
Limitations and Future Directions
The study was cross-sectional, meaning it captured a single time point rather than following patients over time. The natalizumab group was relatively small, limiting the ability to detect subtle differences.
Future longitudinal studies with larger cohorts could clarify whether adipocytokine shifts predict relapses, disability progression, or long-term treatment outcomes. Incorporating metabolic measures like insulin sensitivity and lipid profiles could further refine the picture.
Takeaway: Linking Fat, Immunity, and MS Therapy
This research adds to growing evidence that immune and metabolic health are tightly intertwined in MS. The adipocytokines adiponectin, visfatin, and resistin appear to respond differently to MS treatments, hinting that monitoring them could one day complement MRI scans and clinical exams.
In particular, natalizumab’s boost in adiponectin underscores its role not only in blocking immune cell entry into the brain but also in reshaping systemic inflammatory balance. Fingolimod, by contrast, shows a more nuanced and BMI-dependent effect on adipocytokines.
As MS care moves toward precision medicine, tracking fat-derived messengers may become an unexpected but valuable tool in tailoring therapies.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Adamczyk, B., Morawiec, N., Kwinta, R., Rakoca, M., Wawrzyniak, S., Zalejska-Fiolka, J., Sowa, A., Sawa, K., & Adamczyk-Sowa, M. (2025). Evaluation of Selected Serum Adipocytokines in Patients with Relapsing–Remitting Multiple Sclerosis Treated with Immunomodulatory Second-Line Drugs. International Journal of Molecular Sciences, 26(16), 8070. https://doi.org/10.3390/ijms26168070
