Fatty acid binding protein-4 is associated with disability in multiple sclerosis patients

Abstract

Background:

Increased adiposity is a risk factor for multiple sclerosis (MS) and is associated with increased disability scores. Adipokines may mediate the effects of adiposity on MS disease course.

Objective:

The objective of this study is to examine the association between the adipokines (leptin and fatty acid binding protein-4, FABP4) and clinical course in individuals with MS.

Methods:

Subjects (18–65 years) with relapsing-remitting MS or clinically isolated syndrome and <10 year disease duration were selected from a longitudinal clinical study. Cross-sectional and longitudinal models assessed the relationship between two adipokines (leptin and FABP4) and disease severity in women and men, adjusting for age, disease duration and disease type, Vitamin D level, testosterone level, and as well by body mass index (BMI).

Results:

Mean age of subjects (N = 163, 56% women) was 39.3 years. Higher FABP4 levels were associated with higher Expanded Disability Status Scale (EDSS) scores in women in both univariate and multivariate analyses (odds ratio: 1.30; p = 0.005). In men, higher FABP4 level was significantly associated with change in EDSS over time (estimate: 0.0062; p = 0.035). We found no association of FABP4 levels with time to next relapse or a measure of processing speed.

Conclusion:

FABP4 levels may be associated with increased disability in both men and women with MS independent of effects of BMI and other hormones. Future studies should expand these analyses and further explore downstream mechanisms of adiposity-related effects in MS.

Keywords

Body mass index leptin fatty acid binding protein gender multiple sclerosis

Get full access to this article

View all access options for this article.

References

Munger

Chitnis

Ascherio

Body size and risk of MS in two cohorts of US women. Neurology 2009; 73: 1543–1550.

Hedstrom

Olsson

Alfredsson

High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Mult Scler 2012; 18: 1334–1336.

Munger

Bentzen

Laursen

et al . Childhood body mass index and multiple sclerosis risk: A long-term cohort study. Mult Scler 2013; 19: 1323–1329.

Hedstrom

Lima Bomfim

Barcellos

et al . Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis. Neurology 2014; 82: 865–872.

Langer-Gould

Brara

Beaber

et al . Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology 2013; 80: 548–552.

Chitnis

Graves

Weinstock-Guttman

et al . Distinct effects of obesity and puberty on risk and age at onset of pediatric MS. Ann Clin Transl Neurol 2016; 3: 897–907.

Bove

Musallam

Xia

et al . Longitudinal BMI trajectories in multiple sclerosis: Sex differences in association with disease severity. Mult Scler Relat Disord 2016; 8: 136–140.

Matarese

Carrieri

Montella

et al . Leptin as a metabolic link to multiple sclerosis. Nat Rev Neurol 2010; 6: 455–461.

Hietaharju

Kuusisto

Nieminen

et al . Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: A Finnish co-twin study. Eur J Neurol 2010; 17: 332–334.

10.

Kraszula

Jasinska

Eusebio

et al . Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis. Neurol Neurochir Pol 2012; 46: 22–28.

11.

Matarese

Carrieri

La Cava

et al . Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci U S A 2005; 102: 5150–5155.

12.

Emamgholipour

Eshaghi

Hossein-nezhad

et al . Adipocytokine profile, cytokine levels and foxp3 expression in multiple sclerosis: A possible link to susceptibility and clinical course of disease. PLoS ONE 2013; 8: e76555.

13.

Evangelopoulos

Koutsis

Markianos

Serum leptin levels in treatment-naive patients with clinically isolated syndrome or relapsing-remitting multiple sclerosis. Autoimmune Dis 2014; 2014: 486282.

14.

Ishimura

Furuhashi

Watanabe

et al . Circulating levels of fatty acid-binding protein family and metabolic phenotype in the general population. PLoS ONE 2013; 8: e81318.

15.

Messina

Vargas-Lowy

Musallam

et al . Increased leptin and A-FABP levels in relapsing and progressive forms of MS. BMC Neurol 2013; 13: 172.

16.

Bove

Musallam

Healy

et al . Low testosterone is associated with disability in men with multiple sclerosis. Mult Scler 2014; 20: 1584–1592.

17.

Bove

Chitnis

The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler 2014; 20: 520–526.

18.

Gauthier

Glanz

Mandel

et al . A model for the comprehensive investigation of a chronic autoimmune disease: The multiple sclerosis CLIMB study. Autoimmun Rev 2006; 5: 532–536.

19.

Polman

Reingold

Edan

et al . Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol 2005; 58: 840–846.

20.

Bhasin

Pencina

Jasuja

et al . Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham heart study and applied to three geographically distinct cohorts. J Clin Endocrinol Metab 2011; 96: 2430–2439.

21.

Munger

Levin

Hollis

et al . Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832–2838.

22.

Tanamas

Lean

Combet

et al . Changing guards: Time to move beyond body mass index for population monitoring of excess adiposity. QJM 2016; 109: 443–446.

23.

Simon

Roth

Gordon

JI.

Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. J Biol Chem 1993; 268: 18345–18358.

24.

Epstein

Bass

Iwahara

et al . Immunological identity of rat liver cytosolic heme-binding protein with purified and recombinant liver fatty acid binding protein by western blots of two-dimensional gels. Biochem Biophys Res Commun 1994; 204: 163–168.

25.

Furuhashi

Fucho

Gorgun

et al . Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest 2008; 118: 2640–2650.

26.

Luo

Lopes-Virella

et al . The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis 2002; 165: 259–269.

27.

Tso

Cheung

et al . Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: A 5-year prospective study. Circulation 2007; 115: 1537–1543.

28.

Tso

Lam

et al . Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death. Neurology 2011; 76: 1968–1975.

29.

Hui

Zhou

et al . Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1. J Biol Chem 2010; 285: 10273–10280.

30.

Rao

Singh

et al . Targeting epidermal fatty acid binding protein for treatment of experimental autoimmune encephalomyelitis. BMC Immunol 2015; 16: 28.

31.

Uher

Fellows

Horakova

et al . Serum lipid profile changes predict neurodegeneration in interferon-beta1a-treated multiple sclerosis patients. J Lipid Res 2017; 58: 403–411.

32.

Weinstock-Guttman

Zivadinov

Mahfooz

et al . Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation 2011; 8: 127.

33.

Tettey

Simpson

Taylor

et al . An adverse lipid profile and increased levels of adiposity significantly predict clinical course after a first demyelinating event. J Neurol Neurosurg Psychiatry 2017; 88: 395–401.

34.

Turer

Lin

Flores

Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics 2013; 131: e152–e161.

35.

Simon

Munger

Ascherio

Vitamin D and multiple sclerosis: Epidemiology, immunology, and genetics. Curr Opin Neurol 2012; 25: 246–251.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.33 MB