Multiple sclerosis and obesity: The role of adipokines

Abstract

Multiple Sclerosis (MS), a chronic inflammatory disease of the central nervous system that leads to demyelination and neurodegeneration has been associated with various environmental and lifestyle factors. Population-based studies have provided evidence showing the prevalence of MS is increasing worldwide. Because a similar trend has been observed for obesity and metabolic syndrome, interest has grown in possible underlying biological mechanisms shared by both conditions. Adipokines, a family of soluble factors produced by adipose tissue that participate in a wide range of biological functions, contribute to a low state of chronic inflammation observed in obesity, and influence immune function, metabolism, and nutritional state. In this review, we aim to describe epidemiological and biological factors common to MS and obesity, as well as provide an update on current knowledge of how different pro- and anti-inflammatory adipokines participate as immune response mediators in MS, as well as in the animal model for MS, namely, experimental autoimmune encephalomyelitis (EAE). Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination, and neurodegeneration. Although its pathogenesis is not yet fully understood, there is considerable evidence to suggest MS arises from complex interactions between individual genetic susceptibility and external environmental factors. In recent decades, population-based studies have provided evidence indicating the prevalence of MS is increasing worldwide, in parallel with the rise in obesity and metabolic syndrome. This synchronous increment in the incidence of both MS and obesity has led to a search for potential biological mechanisms linking both conditions. Notably, a large number of studies have established significant correlation between obesity and higher prevalence, or worse prognosis, of several immune-mediated conditions. Fat tissue has been found to produce a variety of soluble factors named adipokines. These mediators, secreted by both adipocytes as well as diverse immune cells, participate in a wide range of biological functions, further strengthening the concept of a link between immune function, metabolism, and nutritional state. Because obesity causes overproduction of pro-inflammatory adipokines (namely leptin, resistin and visfatin) and reduction of anti-inflammatory adipokines (adiponectin and apelin), adipose tissue dysregulation would appear to contribute to a state of chronic, low-grade inflammation favoring the development of disease. In this review, we present a summary of current knowledge related to the pathological effects of different adipokines, prevalent in obese MS patients.

Systemic lupus erythematosus is associated with lower risk of hepatitis B virus infection: A multivariable Mendelian randomization study in East Asian population

“…The impact of obesity on the development and progression of autoimmune diseases has been established in prior research 43,44 . Additionally, RA, as an autoimmune disease, often cooccurs with SLE 45 .…”

“…The impact of obesity on the development and progression of autoimmune diseases has been established in prior research. 43,44 Additionally, RA, as an autoimmune disease, often cooccurs with SLE. 45 Given multiple exposures and effectors, to further ascertain the causal relationship between SLE and HBV, we included BMI and RA in a multivariable MR analysis.…”

Dietary Polyphenols, Microbiome, and Multiple Sclerosis: From Molecular Anti-Inflammatory and Neuroprotective Mechanisms to Clinical Evidence

“…Being overweight/obesity is associated with a low-level chronic inflammatory state which could be a contributing risk factor in some neuroinflammatory diseases like MS [ 92 ]. Dietary nutrients can interact with multiple enzymes, transcription factors, and receptors, inducing physiological and metabolic (catabolic or anabolic) cellular responses.…”

Serum levels of adipokines and insulin are associated with markers of brain atrophy and cognitive decline in the spectrum of Alzheimer’s Disease

“…Moreover, leptin resistance might also facilitate chronic inflammation (Martin, Qasim, and Reilly 2008). When levels of leptin are consistently high, leptin creates a pro-inflammatory effect by increasing the proliferative activity of macrophages and by stimulating the secretion of the cytokines interleukin 6 (IL6), interleukin 1 beta (IL1β), and tumor necrosis factor alpha (TNFα) (Correale and Marrodan 2022; Martin, Qasim, and Reilly 2008). Due to these proinflammatory effects, high concentrations of leptin are largely regarded as detrimental for cerebrovascular disease, and can contribute to the formation of the atherosclerotic plaques (Liu et al 2022; Reilly et al 2004).…”

“…Adiponectin is an anti-inflammatory peptide secreted exclusively in the white adipose tissue. It inhibits the maturation and proliferation of macrophages and the secretion of TNFα and interferons, while at the same time it increases the secretion of anti-inflammatory cytokines, such as TNFβ and IL10 (Correale and Marrodan 2022). Low adiponectin has been associated with increases in cardiometabolic burden, with type 2 diabetes mellitus, and with abdominal obesity (Forny-Germano, De Felice, and Vieira 2018).…”