Adipokines as Immune Cell Modulators in Multiple Sclerosis

Abstract

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.

The Role of Diet and Interventions on Multiple Sclerosis: A Review

“…This condition leads to a pro-inflammatory status increasing levels of interleukin 6 (IL-6), TNF-alpha, and leptin, factors that are associated with MS pathogenesis [ 41 ]. Additionally, recent studies suggest that increased BMI and obesity play a major role in MS development and progression [ 42 ]. Obesity and MS can lead to altered adipokine release into the blood circulation.…”

“…This activates inflammatory pathways and increases the infiltration of immune cells in the CNS. Moreover, increased levels of pro-inflammatory cytokines in MS release pro-inflammatory adipokines and disrupt adipokine pathway, creating a feedback loop [ 42 ]. Pathophysiologically, obesity affects MS by promoting chronic inflammation, altering the endocrine system by disturbing the secretion of adipokines and influencing the gut microbiota [ 42 ].…”

“…Moreover, increased levels of pro-inflammatory cytokines in MS release pro-inflammatory adipokines and disrupt adipokine pathway, creating a feedback loop [ 42 ]. Pathophysiologically, obesity affects MS by promoting chronic inflammation, altering the endocrine system by disturbing the secretion of adipokines and influencing the gut microbiota [ 42 ]. Moreover, an unbalanced diet contributes to an increase in BMI and abdominal obesity.…”

“…Overweight and obesity are associated with chronic inflammation of adipose tissue, which is accompanied by an altered secretion of adipokines. These adipokines are hormones and cytokines that regulate metabolic pathways [ 42 ]. Among others, leptin and adiponectin seem to be associated with the pathogenesis of MS. Leptin regulates energy and acute phase reactions, interfering in the activity and progression of experimental autoimmune encephalomyelitis (EAE) in mice or the pathogenesis of MS in humans [ 26 ].…”

Lifestyle and health of individuals with multiple sclerosis according to body mass index: initial results

“…IL-6, IL-1β, TNF-α, IFN-γ, and CRP); disrupted adipokine production (e.g. leptin and adiponectin); and changes in the intestinal microbiome [10][11][12]. Furthermore, some authors have indicated that obesity may increase the risk of MS, leading to a decreased bioavailability of vitamin D, while in turn, a low concentration of vitamin D correlates with a pro-inflammatory state [13,14].…”