Adipokines are associated with pediatric multiple sclerosis risk and course

Keyhanian, Kiandokht; Saxena, Shrishti; Gombolay, Grace; Healy, Brian C.; Misra, Madhusmita; Chitnis, Tanuja

doi:10.1016/j.msard.2019.101384

Cited by 21 publications

(22 citation statements)

References 27 publications

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“…32 While some observational studies have described increased leptin and lowered adiponectin levels in MS compared to controls, these have generally been small and included prevalent MS cases, making them susceptible to reverse causality. 4 That said, small effects by those cytokines on MS risk may still exist given their wider estimate confidence intervals.…”

Section: Discussionmentioning

confidence: 99%

The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis

et al. 2021

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Background: Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear. Objective: To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS. Methods: We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls. We then estimated the proportion of the effect of obesity on MS explained by these potential mediators. Results: Genetic predisposition to higher BMI was associated with increased MS risk (odds ratio (OR) = 1.33 per standard deviation (SD), 95% confidence interval (CI) = 1.09–1.63), while higher 25OHD levels reduced odds of MS (OR = 0.72 per SD, 95% CI = 0.60–0.87). In contrast, we observed no effect of adiponectin or leptin. In MR mediation analysis, 5.2% of the association between BMI and MS was attributed to obesity lowering 25OHD levels (95% CI = 0.3%–31.0%). Conclusions: This study found that a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect. Consequently, vitamin D supplementation would only modestly reverse the effect of obesity on MS.

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Section: Discussionmentioning

confidence: 99%

The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis

et al. 2021

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“…At the same time, new evidence shows blood–brain-barrier (BBB) changes in obesity (probably similar to BBB alterations in MS), promoting the idea that leptin resistance is caused by the affected transport of leptin at BBB level (Pan and Myers, 2018) [ 39 ]. This pathophysiological theory is supported by clinical results, with a relevant example being the study of Keyhanian et al, 2019, that showed an increased level of leptin in patients with pediatric MS [ 40 ].…”

Section: Common Pathophysiological Elements For Obesity and Multiple Sclerosismentioning

confidence: 94%

Obesity and Multiple Sclerosis—A Multifaceted Association

Schreiner

Genes

2021

JCM

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Background: Given the common elements in the pathophysiological theories that try to explain the appearance and evolution of obesity and multiple sclerosis, the association between the two pathologies has become an increasingly researched topic in recent years. On the one hand, there is the chronic demyelinating inflammation caused by the autoimmune cascade of multiple sclerosis, while on the other hand, according to the latest research, it has been shown that obesity shares an inflammatory component with most chronic diseases. Methods: The authors performed independent research of the available literature in the most important electronic databases (PubMed, Google Scholar, Embase, and Science Direct) in February 2021. After applying the exclusion criteria, the reviewers focused on the most relevant articles published during the last 10 years with respect to epidemiology and pathophysiology. Results: The data presented are a step forward in trying to elucidate the intricate relationship between obesity and MS, especially the causal relationship between childhood and adolescent obesity and MS, focusing on the epidemiological associations observed in the most relevant observational studies conducted in recent years. In the second part, the authors comment on the latest findings related to the pathophysiological mechanisms that may explain the correlations between obesity and multiple sclerosis, focusing also on the role of adipokines. Conclusions: Based on available epidemiological data, obesity in early life appears to be strongly associated with a higher risk of MS development, independent of other risk factors. Although much research has been done on the pathophysiology of obesity, MS, their possible common mechanism, and the role of adipokines, further studies are needed in order to explain what remains unknown. No relevant data were found regarding the association between obesity, disability (high EDSS score), and mortality risk in MS patients. Thus, we consider that this topic should be elucidated in future research.

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“…The overlapping inflammation-related signature suggests RIPK1 signaling in CNS cells may regulate various cytokines and chemokines implicated in MS pathogenesis (Figure 4J; Gö bel et al, 2018;Jafarzadeh et al, 2014;Khaibullin et al, 2017;Li et al, 2017;Ofengeim et al, 2017;Seppi et al, 2014;Soleimani et al, 2019). Genes involved in lipid signaling and metabolism previously linked to MS and its progression were modulated in a RIPK1-kinasedependent manner in astrocytes and microglia (Figure 4K; International Multiple Sclerosis Genetics Conssortium (IMSGC), 2010; Al Nimer et al, 2016;Bove et al, 2019;Forwell et al, 2016;Keyhanian et al, 2019;Lee and Bou Dagher, 2016). Because our RNA-seq data identified multiple genes linked to cholesterol signaling and function, we assessed the role of RIPK1 in modulating lipid metabolism by performing lipidomic analysis of sterols in astrocytes.…”

Section: Ripk1 Signaling In Astrocytes Drives a Disease-relevant Gene Signaturementioning

confidence: 99%

RIPK1 activation mediates neuroinflammation and disease progression in multiple sclerosis

et al. 2021

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Adipokines are associated with pediatric multiple sclerosis risk and course

Cited by 21 publications

References 27 publications

The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis

The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis

Obesity and Multiple Sclerosis—A Multifaceted Association

RIPK1 activation mediates neuroinflammation and disease progression in multiple sclerosis

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