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BMC Neurology
Published in: BMC Neurology 1/2013

Open Access 01-12-2013 | Research article

Increased leptin and A-FABP levels in relapsing and progressive forms of MS

Authors: Silvia Messina, David Vargas-Lowy, Alexander Musallam, Brian C Healy, Pia Kivisakk, Roopali Gandhi, Riley Bove, Taha Gholipour, Samia Khoury, Howard L Weiner, Tanuja Chitnis

Published in: BMC Neurology | Issue 1/2013

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Abstract

Background

Leptin and adipocyte-fatty acid binding protein (A-FABP) are produced by white adipose tissue and may play a role in chronic inflammation in Multiple Sclerosis (MS). To assess leptin and A-FABP in relapsing and progressive forms of MS.

Methods

Adipokine levels were measured in untreated adult relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and Healthy control (HC). Pediatric-onset MS (POMS) and pediatric healthy controls (PHC) were also assessed. Leptin and A-FABP levels were measured in serum by ELISA. Groups were compared using linear mixed-effects model.

Results

Excluding two patients with Body Mass Index (BMI) > 50, a significant difference in leptin level was found between RRMS and HC controlling for age (p = 0.007), SPMS and HC controlling for age alone (p = 0.002), or age and BMI (p = 0.007). A-FABP levels were higher in SPMS than HC (p = 0.007), controlling for age and BMI. Differences in A-FABP levels between POMS and PHC was observed after controlling for age (p = 0.019), but not when BMI was added to the model (p = 0.081).

Conclusion

Leptin and A-FABP levels are highest in SPMS compared to HC, suggesting a role in pathogenesis of this disease subtype. A-FABP levels are increased in POMS patients and may play a role in the early stages of disease.
Appendix
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Literature
1.
Weiner HL: A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis. J Neurol. 2008, 255 (Suppl 1): 3-11.CrossRefPubMed
2.
Ouchi N, Ohashi K, Shibata R, Murohara T: Adipocytokines and obesity-linked disorders. Nagoya J Med Sci. 2012, 74: 19-30.PubMedPubMedCentral
3.
4.
Tilg H, Moschen AR: Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006, 6: 772-783. 10.1038/nri1937.CrossRefPubMed
5.
Sanna V, Di Giacomo A, La Cava A, et al: Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J Clin Investig. 2003, 111: 241-250.CrossRefPubMedPubMedCentral
6.
7.
Chatzantoni K, Papathanassopoulos P, Gourzoulidou E, Mouzaki A: Leptin and its soluble receptor in plasma of patients suffering from remitting-relapsing multiple sclerosis (MS) In vitro effects of leptin on type-1 and type-2 cytokine secretion by peripheral blood mononuclear cells, T-cells and monocytes of MS patients. J Autoimmun. 2004, 23: 169-177. 10.1016/j.jaut.2004.05.007.CrossRefPubMed
8.
Batocchi AP, Rotondi M, Caggiula M, et al: Leptin as a marker of multiple sclerosis activity in patients treated with interferon-beta. J Neuroimmunol. 2003, 139: 150-154. 10.1016/S0165-5728(03)00154-1.CrossRefPubMed
9.
Angelucci F, Mirabella M, Caggiula M, et al: Evidence of involvement of leptin and IL-6 peptides in the action of interferon-beta in secondary progressive multiple sclerosis. Peptides. 2005, 26: 2289-2293. 10.1016/j.peptides.2005.03.037.CrossRefPubMed
10.
Kazemi MR, McDonald CM, Shigenaga JK, Grunfeld C, Feingold KR: Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arterioscler Thromb Vasc Biol. 2005, 25: 1220-1224. 10.1161/01.ATV.0000159163.52632.1b.CrossRefPubMed
11.
Tso AW, Lam TK, Xu A, et al: Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death. Neurology. 2011, 76: 1968-1975. 10.1212/WNL.0b013e31821e54b3.CrossRefPubMed
12.
Gauthier SA, Glanz BI, Mandel M, Weiner HL: A model for the comprehensive investigation of a chronic autoimmune disease: the multiple sclerosis CLIMB study. Autoimmun Rev. 2006, 5: 532-536. 10.1016/j.autrev.2006.02.012.CrossRefPubMed
13.
Polman CH, Reingold SC, Edan G, et al: Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005, 58: 840-846. 10.1002/ana.20703.CrossRefPubMed
14.
Krupp LB, Banwell B, Tenembaum S: Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology. 2007, 68: S7-S12. 10.1212/01.wnl.0000259422.44235.a8.CrossRefPubMed
15.
Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T: Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009, 66: 54-59.CrossRefPubMed
16.
Pinheiro JC, Bates DM: Mixed-effects models in S and S-PLUS. 2000, New York: Springer, xvi-528.CrossRef
17.
NHLBI Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Obesity in Adults (US): Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Am J Clin Nutr. 1998, 68: 899-917.
18.
Flegal KM, Carroll MD, Kit BK, Ogden CL: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. Jama. 2012, 307: 491-497. 10.1001/jama.2012.39.CrossRefPubMed
19.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature. 1994, 372: 425-432. 10.1038/372425a0.CrossRefPubMed
20.
Friedman JM, Halaas JL: Leptin and the regulation of body weight in mammals. Nature. 1998, 395: 763-770. 10.1038/27376.CrossRefPubMed
21.
Matarese G, Procaccini C, De Rosa V: The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis?. J Leukoc Biol. 2008, 84: 893-899. 10.1189/jlb.0108022.CrossRefPubMed
22.
Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI: Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998, 394: 897-901. 10.1038/29795.CrossRefPubMed
23.
Loffreda S, Yang SQ, Lin HZ, et al: Leptin regulates proinflammatory immune responses. Faseb J. 1998, 12: 57-65.PubMed
24.
Matarese G, Di Giacomo A, Sanna V, et al: Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol. 2001, 166: 5909-5916.CrossRefPubMed
25.
Komori M, Matsuyama Y, Nirasawa T, et al: Proteomic pattern analysis discriminates among multiple sclerosis-related disorders. Ann Neurol. 2012, 71: 614-623. 10.1002/ana.22633.CrossRefPubMed
26.
Frisullo G, Mirabella M, Angelucci F, et al: The effect of disease activity on leptin, leptin receptor and suppressor of cytokine signalling-3 expression in relapsing-remitting multiple sclerosis. J Neuroimmunol. 2007, 192: 174-183. 10.1016/j.jneuroim.2007.08.008.CrossRefPubMed
27.
Chmurzynska A: The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet. 2006, 47: 39-48. 10.1007/BF03194597.CrossRefPubMed
28.
Xu A, Tso AW, Cheung BM, 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. 10.1161/CIRCULATIONAHA.106.647503.CrossRefPubMed
29.
Weinstock-Guttman B, Zivadinov R, Horakova D, et al: Lipid profiles are associated with lesion formation over 24 months in interferon-beta treated patients following the first demyelinating event. J Neurol Neurosurg Psychiatry. 2013
30.
Hui X, Li H, Zhou Z, 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. 10.1074/jbc.M109.097907.CrossRefPubMedPubMedCentral
31.
Reynolds JM, Liu Q, Brittingham KC, et al: Deficiency of fatty acid-binding proteins in mice confers protection from development of experimental autoimmune encephalomyelitis. J Immunol. 2007, 179: 313-321.CrossRefPubMed
32.
Kiess W, Muller G, Galler A, et al: Body fat mass, leptin and puberty. J Pediatr Endocrinol Metab. 2000, 13 (Suppl 1): 717-722.PubMed
33.
Quennell JH, Mulligan AC, Tups A, et al: Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology. 2009, 150: 2805-2812. 10.1210/en.2008-1693.CrossRefPubMedPubMedCentral
34.
Hedstrom AK, Olsson T, Alfredsson L: 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. 10.1177/1352458512436596.CrossRefPubMed
35.
Langer-Gould A, Brara SM, Beaber BE, Koebnick C: Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology. 2013, 80: 548-552. 10.1212/WNL.0b013e31828154f3.CrossRefPubMedPubMedCentral
36.
Lee K, Santibanez-Koref M, Polvikoski T, Birchall D, Mendelow AD, Keavney B: Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture. Atherosclerosis. 2013, 226: 74-81. 10.1016/j.atherosclerosis.2012.09.037.CrossRefPubMedPubMedCentral
37.
Simon C, Gronfier C, Schlienger JL, Brandenberger G: Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: relationship to sleep and body temperature. J Clin Endocrinol Metab. 1998, 83: 1893-1899. 10.1210/jc.83.6.1893.CrossRefPubMed
Metadata
Title
Increased leptin and A-FABP levels in relapsing and progressive forms of MS
Authors
Silvia Messina
David Vargas-Lowy
Alexander Musallam
Brian C Healy
Pia Kivisakk
Roopali Gandhi
Riley Bove
Taha Gholipour
Samia Khoury
Howard L Weiner
Tanuja Chitnis
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2013
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-13-172

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