Lipids at the Cross-road of Autoimmunity in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by demyelination and neurodegeneration, driven by a Th17/Th1-immune response, which afflicts mainly young women. Although MS causes are not completely known, it is notorious that the disease is characterized by an extended focal degradation of the myelin sheath, with ulterior axonal and neuronal damage. Lipid molecules play a main dual role in MS, both as target molecules of myelin destruction and as mediators of inflammation. Indeed, recent cumulative evidence suggests that abnormalities in the lipidbinding proteins of myelin and sphingolipid content that confer increased immunogenicity may underlie the autoimmune response against the myelin sheath. CNS is after all, the second organ richer in lipid content after adipose tissue. On the other hand, soluble factors called adipokines, secreted by adipose tissue, modulate inflammatory responses and contribute to metabolic dysfunction, which may be important in MS pathophysiology. Disability accumulation in MS patients is slow but persistent, often leading to a decreased mobility and physical activity, resulting in more weakness, fatigue and associated increased risk of the metabolic syndrome (MetS). In turn, MetS may trigger MS in susceptible individuals and is a bad prognostic factor. Here we review what are the facts linking lipids, MetS and MS, what we do not know yet, and what we should do to move this field forward.