Is Obesity a Modifiable Risk Factor in Multiple Sclerosis? Mechanistic Insights into Neuroinflammation and Oxidative Damage

<b>Introduction</b>: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS) that leads to demyelination of CNS neurons and is influenced by genetic, environmental, and lifestyle factors, including diet and obesity. <b>Methods</b>: This review aims to analyze at the molecular level the relationship between obesity, as a chronic inflammatory condition, and the pathophysiology of MS, as a chronic autoimmune inflammatory disease, in order to understand the complex links between obesity and MS through a search of the PubMed and Google Scholar databases. <b>Discussion</b>: Chronic inflammation and OS are interconnected processes, causing a toxic state, which contributes to the development of CNS neuroinflammation and neuronal damage, resulting in neuronal demyelination and the onset of MS. Adipose tissue is a complex endocrine organ; in addition to being a lipid storage organ, it secretes cytokines and adipokines, which are involved in the regulation of hormones, metabolism, inflammation, and whole-body homeostasis. Obesity triggers chronic low-grade inflammation, disruption of the blood-brain barrier (BBB) and brain metabolism, infiltration of the CNS by immune cells, production of ROS, and generation of oxidative stress (OS). Anti-inflammatory and pro-inflammatory adipokines are also implicated in MS and obesity. <b>Conclusions</b>: Obesity affects MS through common underlying mechanisms and seems to be a modifiable risk factor. Antioxidant and anti-inflammatory compounds with multi-functional characteristics could be additional tools to slow the progression of MS and its promotion through obesity while also offering potential treatment options for both conditions via their multi-targeting characteristics.