Obesity worsens central inflammation and disability in multiple sclerosis

Bassi, Mario Stampanoni; Iezzi, Ennio; Buttari, Fabio; Gilio, Luana; Simonelli, Ilaria; Carbone, Fortunata; Micillo, Teresa; Rosa, Veronica De; Sica, Francesco; Furlan, Roberto; Finardi, Annamaria; Fantozzi, Roberta; Storto, Marianna; Bellantonio, Paolo; Pirollo, Pamela; Lemme, Sonia Di; Musella, Alessandra; Mandolesi, Georgia; Centonze, Diego; Matarese, Giuseppe

doi:10.1177/1352458519853473

Cited by 82 publications

(63 citation statements)

References 43 publications

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“…However, in several studies conducted in a population of MS patients, there was a positive correlation between the degree of physical disability and the BMI. [47][48][49] The inverse impact of the BMI on physical disability was also recorded in the research of Flauzino et al 50 In several studies as well as in the present one, it was shown that BMI may be considered as a factor that can change during the progression of the disease and that there was an increased incidence of lower values of this parameter with the progression of the disease ie with the transition from RR to SP form. 39 Obesity, among other factors such as gender, age, genetic profile and smoking, has a disease-modifying effect by forming its phenotypic presentation and contributes to the occurrence and progression of MS. 51,52 Research performed at the molecular level showed that high BMI negatively affected the course and form of MS, since the existence of obesity leads to a modulation of the number of monocytes through the ceramide-induced DNA methylation of the antiproliferative genes.…”

Section: Resultssupporting

confidence: 81%

Association of body mass index with progression and prediction of multiple sclerosis

Tadić¹,

Đajić²,

Grgić³

et al. 2020

Scripta Medica

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Background/Aim: Multiple sclerosis is a disease whose aetiology involves multifactorial interactions among genetic and environmental factors. Obesity is one of the most important environmental factors conducive to the onset and progression of the disease. The aim of the study was to determine the value of body mass index (BMI) in a population of patients with multiple sclerosis compared to the general population, in order to assess the relation between the BMI and physical disability in patients with multiple sclerosis and the influence of the BMI on the course and progression of the disease. Methods: A cross-sectional study was performed in 100 patients suffering from multiple sclerosis (experimental group) and 50 healthy people (control group). In order to determine the degree of physical disability, the Expanded Disability Status Scale (EDSS) was used. Clinical and demographic data and values of the BMI in both studied groups were collected. Statistical analysis included the descriptive statistics, t-test, chi-square test, analysis of variance, correlation and regression analysis. Results: Mean body weight and BMI were significantly higher in the control group (p< 0.05). There was no significant correlation between EDSS and BMI (p = 0.574). There was a correlation between the course of MS and the fact whether BMI was abnormal or normal (p = 0.031). Conclusion: BMI is an environmental factor that significantly correlates with the progression and prediction of multiple sclerosis, but not to the degree of physical disability.

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Section: Resultssupporting

confidence: 81%

Association of body mass index with progression and prediction of multiple sclerosis

Tadić¹,

Đajić²,

Grgić³

et al. 2020

Scripta Medica

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“…Adipose tissue, once regarded solely as a tissue that stores fat and serves a protective role, is now recognized as an organ with many significant physiological functions 1 , such as inflammation and tissue repair 2 , and endocrine functions 3 . It is well known that obese people and animals have high levels of proinflammatory cytokines, such as serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL)-1β, IL-6, and IL-17 all of which are produced by macrophages derived from adipose tissue 4 , 5 . Adipose tissue constitutes the major source of cytokines, chemokines, and metabolically active mediators known as adipokines 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Brown adipose tissue ameliorates autoimmune arthritis via inhibition of Th17 cells

Moon

Kim

et al. 2020

Sci Rep

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The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA). Some studies have shown that the three compositions of adipose tissue (white, brown, and beige) have different functions. Brown adipose tissue (BAT) is known to secrete several factors that differ from those in white adipose tissue. This suggests that BAT might have potential positive advantages in the physiology of autoimmune diseases. We compared the functions of collageninduced arthritis mice-derived BAT (CIA BAT) with normal mice-derived BAT. DBA/1J mice (6-7 weeks of age) were immunized by intradermal injection at the base of the tail with 100 μg of bovine type II collagen (CII) emulsified in complete Freund's adjuvant. Immunized mice then received booster immunizations by intraperitoneal injection with 100 μg of CII in incomplete Freund's adjuvant. We transplanted CIA BAT and normal BAT into CIA recipient mice. After transplantation, we measured the functions of CIA BAT and normal BAT in mice. Normal BAT-transplanted mice showed significantly lower scores of bone damage, inflammation, and cartilage damage. The proinflammatory cytokines in normal BAT-transplanted mice, such as IL-12, IL-17, IL-6, and tumor necrosis factor-α (TNF-α), tended to decrease. Microarray analysis showed that the PI3K-AKT signaling pathway and IL-17 levels of CIA BAT tissues were significantly higher than those of normal BAT tissues. These results suggest that the transplantation of normal brown fat may have a therapeutic effect in RA patients. Adipose tissue, once regarded solely as a tissue that stores fat and serves a protective role, is now recognized as an organ with many significant physiological functions 1 , such as inflammation and tissue repair 2 , and endocrine functions 3. It is well known that obese people and animals have high levels of proinflammatory cytokines, such as serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL)-1β, IL-6, and IL-17 all of which are produced by macrophages derived from adipose tissue 4,5. Adipose tissue constitutes the major source of cytokines, chemokines, and metabolically active mediators known as adipokines 6,7. It has been suggested that inflammation, which is induced by adipose tissue, is associated with osteoarthritis 8-10 , rheumatoid arthritis (RA) 11-13 , type 2 diabetes mellitus 14-17 , and coronary artery disease 18,19. RA is linked with most components of metabolic syndromes, such as changes in body weight, dyslipidemia, adipokine resistance, and insulin resistance 20. Some studies have shown that obesity elevates the expression levels of proinflammatory cytokines and reduces the expression levels of anti-inflammatory cytokines 21,22. Notably,

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“…Altered lipid profiles have been associated with poor outcome of multiple sclerosis (MS) (75)(76)(77)(78)(79)(80), an autoimmune disease characterized by inflammatory cell infiltrates and demyelination (81,82). In this regard, obesity, among other environmental factors, has been described as a risk factor for MS in several epidemiological studies (83)(84)(85)(86).…”

Section: Lxrs and Autoimmunitymentioning

confidence: 99%

Liver X Receptors: Regulators of Cholesterol Metabolism, Inflammation, Autoimmunity, and Cancer

et al. 2020

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The interplay between cellular stress and immune response can be variable and sometimes contradictory. The mechanisms by which stress-activated pathways regulate the inflammatory response to a pathogen, in autoimmunity or during cancer progression remain unclear in many aspects, despite our recent knowledge of the signalling and transcriptional pathways involved in these diseases. In this context, over the last decade many studies demonstrated that cholesterol metabolism is an important checkpoint for immune homeostasis and cancer progression. Indeed, cholesterol is actively metabolized and can regulate, through its mobilization and/or production of active derivatives, many aspects of immunity and inflammation. Moreover, accumulation of cholesterol has been described in cancer cells, indicating metabolic addiction. The nuclear receptors liver-X-receptors (LXRs) are important regulators of intracellular cholesterol and lipids homeostasis. They have also key regulatory roles in immune response, as they can regulate inflammation, innate and adaptive immunity. Moreover, activation of LXRs has been reported to affect the proliferation and survival of different cancer cell types that show altered metabolic pathways and accumulation of cholesterol. In this minireview we will give an overview of the recent understandings about the mechanisms through which LXRs regulate inflammation, autoimmunity, and cancer, and the therapeutic potential for future treatment of these diseases through modulation of cholesterol metabolism.

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Obesity worsens central inflammation and disability in multiple sclerosis

Cited by 82 publications

References 43 publications

Association of body mass index with progression and prediction of multiple sclerosis

Association of body mass index with progression and prediction of multiple sclerosis

Brown adipose tissue ameliorates autoimmune arthritis via inhibition of Th17 cells

Liver X Receptors: Regulators of Cholesterol Metabolism, Inflammation, Autoimmunity, and Cancer

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