Adipokines in multiple sclerosis: Immune dysregulation, neuroinflammation, and therapeutic opportunities

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS), characterized by demyelination, neuroinflammation, and the progressive accumulation of neurologic deficits. Adipose tissue secretes predominantly the bioactive molecules, known as adipokines, which have drawn considerable attention for their roles in modulating immune and metabolic pathways in people with MS (PwMS). Dysregulated adipokines, such as resistin, leptin, and chemerin, induce pro-inflammatory T-cell polarization while deteriorating Blood-Brain Barrier (BBB) integrity. Adiponectin, by contrast, has both immunomodulatory and neuroprotective functions. The opposing functionality highlights the biomarker and the therapeutic potential of adipokines. Preclinical and translational findings have shed light on the role of adipokines in the pathophysiology of MS by influencing T-cell, glial, and BBB functions. In clinical settings, the assessment of adipokines can function as an indicator of prognosis and diagnosis via distinct patterns of expression. In addition, alterations to adipokine profiles through lifestyle changes and pharmaceutical treatment may complement established disease-modifying treatments (DMTs). This study has highlighted the multifaceted role of adipokines in MS management, while further studies exploring the role of adipokine-mediated immunometabolic regulation are suggested.