Obesity and adipose tissue-derived cytokines in the pathogenesis of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neurological impairments. The etiology of MS is not clearly understood but genetics and environmental factors can affect the susceptibility of individuals. Obesity or a body mass index of (BMI) > 30 kg/m2 is associated with serious health consequences such as lipid profile abnormalities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D and a systemic low-grade inflammatory state that can affect the CNS and promote the pathogenesis of MS. This is due in part to the increased blood-brain barrier permeability by the actions of adipose tissue-derived cytokines or adipokines. Pro-inflammatory adipokines such as leptin, resistin, and visfatin by crossing the blood-brain barrier activate the CNS-resident immune cells, promote the inflammatory responses, and subsequently, demyelinating lesions occur in the white matter of the brain and spinal cord. Therefore, a better knowledge of the roles of adipokines in the induction of obesity-related chronic inflammation and subsequent events leading to dysfunctional blood-brain barrier is of considerable importance. In this review, recent evidence regarding the possible roles of obesity and its related systemic low-grade inflammation, as well as the roles of adipokines and their genetic variants in the modulation of immune responses and altered blood-brain barrier permeability in MS patients has been elucidated. Besides, the results of the current studies regarding the potential use of adipokines in predicting MS disease severity and response to treatment have been explored.