Multiple Sclerosis: Implications of Obesity in Neuroinflammation

Novo, Ana; Batista, Sónia

doi:10.1007/978-3-319-63260-5_8

Cited by 14 publications

(12 citation statements)

References 96 publications

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“…Several studies have repeatedly shown that obesity is a risk factor for early-onset MS 35–37 . While the underlying mechanism by which obesity contributes to MS etiology remains unclear several hypotheses have been postulated including; the effect of persistent low-grade neuroinflammation 38 , the role of adipose tissue adipokines in promoting inflammation 39 , and obesity-related central nervous system cardiovascular alterations 40 . The role of obesity in MS expands beyond risk as it has been shown to worsen MS disease disability and progression as well 10,13 .…”

Section: Discussionmentioning

confidence: 99%

The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients

Al-Serri

Alroughani

Al-Temaimi

2019

Sci Rep

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Obesity is a well-known risk factor for multiple diseases including multiple sclerosis (MS). Polymorphisms in the fat-mass obesity (FTO) gene have been consistently found to be associated with obesity, and recently found to increase the risk of developing MS. We therefore assessed the common FTO gene polymorphism (rs9939609) in relation to obesity, risk of developing MS and its disability in a cohort of MS patients. A cohort of 200 MS patients (135 females and 65 males) were genotyped for the FTO rs9939609 polymorphism. Using both logistic and linear regression we assessed the relationship between the variant and the selected phenotypes under both an additive and recessive genetic models. The A-allele was found to be associated with being overweight/obese in MS patients (OR = 2.48 (95% CI 1.17–5.29); p = 0.01). In addition, The A-allele was also found to be associated with increased MS disability (β = 0.48 (95% CI 0.03–0.92); p = 0.03). However, no association was found with risk of developing MS (p > 0.05). Moreover, our association with obesity is consistent with previous reports, whereas the association with disability is novel and warrants further investigation on the role of FTO in disease progression.

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Section: Discussionmentioning

confidence: 99%

The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients

Al-Serri

Alroughani

Al-Temaimi

2019

Sci Rep

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“…Obesity, especially in adolescence has been reported to have an effect on MS susceptibility, but it is unclear whether this may be attributed to genetically determined factors or environmental/ socio-economical influences or a combination of different effects, e.g., a low-grade neuro-inflammatory effect or a vitDsequestering effect (50)(51)(52)(53).…”

Section: Ms Etiology and Epidemiologymentioning

confidence: 99%

Epstein-Barr Virus and Multiple Sclerosis

2020

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Multiple sclerosis (MS) is a neurologic disease affecting myelinated nerves in the central nervous system (CNS). The disease often debuts as a clinically isolated syndrome, e.g., optic neuritis (ON), which later develops into relapsing-remitting (RR) MS, with temporal attacks or primary progressive (PP) MS. Characteristic features of MS are inflammatory foci in the CNS and intrathecal synthesis of immunoglobulins (Igs), measured as an IgG index, oligoclonal bands (OCBs), or specific antibody indexes. Major predisposing factors for MS are certain tissue types (e.g., HLA DRB1*15:01), vitamin D deficiency, smoking, obesity, and infection with Epstein-Barr virus (EBV). Many of the clinical signs of MS described above can be explained by chronic/recurrent EBV infection and current models of EBV involvement suggest that RRMS may be caused by repeated entry of EBV-transformed B cells to the CNS in connection with attacks, while PPMS may be caused by more chronic activity of EBV-transformed B cells in the CNS. In line with the model of EBV’s role in MS, new treatments based on monoclonal antibodies (MAbs) targeting B cells have shown good efficacy in clinical trials both for RRMS and PPMS, while MAbs inhibiting B cell mobilization and entry to the CNS have shown efficacy in RRMS. Thus, these agents, which are now first line therapy in many patients, may be hypothesized to function by counteracting a chronic EBV infection.

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“…This issue is of highest relevance given that, so far, modification of vascular risk factors has shown only limited effects to slow the progression of WMH. 20 Systemic inflammation has also been suggested to affect white matter, 21 and circulating cytokines were related to increased WMH volume in several large cohorts. Particularly, the distinction between patchy WMH around the ventricles (periventricular, pvWMH) versus more confluent WMH in the deep white matter (dWMH) may be of relevance.…”

mentioning

confidence: 99%

“…Notably, obesity and visceral fat especially contribute to systemic low‐grade inflammation through release of cytokines such as interleukin‐6 (IL6) and C‐reactive protein (CRP) . Systemic inflammation has also been suggested to affect white matter, and circulating cytokines were related to increased WMH volume in several large cohorts . Thus, low‐grade inflammation could be an independent mechanism of obesity‐related white matter damage.…”

mentioning

confidence: 99%

Visceral obesity relates to deep white matter hyperintensities via inflammation

Lampe

Zhang

Beyer

et al. 2019

Annals of Neurology

132

100

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Objective White matter hyperintensities (WMHs) are linked to vascular risk factors and increase the risk of cognitive decline, dementia, and stroke. We here aimed to determine whether obesity contributes to regional WMHs using a whole‐brain approach in a well‐characterized population‐based cohort. Methods Waist‐to‐hip ratio (WHR), body mass index (BMI), systolic/diastolic blood pressure, hypertension, diabetes and smoking status, blood glucose and inflammatory markers, as well as distribution of WMH were assessed in 1,825 participants of the LIFE‐adult study (age, 20–82 years; BMI, 18.4–55.4 kg/m 2 ) using high‐resolution 3‐Tesla magnetic resonance imaging. Voxel‐wise analyses tested if obesity predicts regional probability of WMH. Additionally, mediation effects of high‐sensitive C‐reactive protein and interleukin‐6 (IL6) measured in blood were related to obesity and WMH using linear regression and structural equation models. Results WHR related to higher WMH probability predominantly in the deep white matter, even after adjusting for effects of age, sex, and systolic blood pressure (mean ß = 0.0043 [0.0008 SE], 95% confidence interval, [0.00427, 0.0043]; threshold‐free cluster enhancement, family‐wise error‐corrected p < 0.05). Conversely, higher systolic blood pressure was associated with WMH in periventricular white matter regions. Mediation analyses indicated that both higher WHR and higher BMI contributed to increased deep‐to‐periventricular WMH ratio through elevated IL6. Interpretation Our results indicate an increased WMH burden selectively in the deep white matter in obese subjects with high visceral fat accumulation, independent of common obesity comorbidities such as hypertension. Mediation analyses proposed that visceral obesity contributes to deep white matter lesions through increases in proinflammatory cytokines, suggesting a pathomechanistic link. Longitudinal studies need to confirm this hypothesis. ANN NEUROL 2019;85:194–203.

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Multiple Sclerosis: Implications of Obesity in Neuroinflammation

Cited by 14 publications

References 96 publications

The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients

The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients

Epstein-Barr Virus and Multiple Sclerosis

Visceral obesity relates to deep white matter hyperintensities via inflammation

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