Abstract
Clinical and experimental data, together with epidemiological studies, have suggested that the pathogenesis of multiple sclerosis (MS) might involve factors that link the immune system with metabolic status. Moreover, recent research has shown that leptin, the adipocyte-derived hormone that controls food intake and metabolism, can promote experimental autoimmune encephalomyelitis, an animal model of MS. In patients with MS, the association of leptin with disease activity has been dissected at the molecular level, providing new mechanistic explanations for the role of this hormone in MS. Here, we review the intricate relationship between leptin and other metabolic modulators within a framework that incorporates the latest advances linking the CNS, immune tolerance and metabolic status. We also consider the translational implications of these new findings for improved management of MS.
Key Points
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Leptin is an adipocyte-derived hormone that is secreted proportionally to adipose tissue mass and inhibits food intake
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Leptin links the immune response to metabolism and nutritional status
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Leptin promotes proinflammatory immune responses and inhibits the proliferation of anti-inflammatory regulatory T cells
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Orexigenic mediators antagonize the anorexigenic and proinflammatory effects of leptin in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS)
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Drugs that affect metabolism are effective at reducing the proinflammatory effects of leptin in EAE
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Given the beneficial effects of leptin blockade on EAE outcome, leptin could represent an attractive target to reduce autoimmune inflammation in MS
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Acknowledgements
G. Matarese is supported by grants from the European Union Ideas Program, ERC-Starting Independent Grant 'LeptinMS' project number 202579 and Telethon-JDRF Grant project number GJT08004. A. La Cava is supported in part by NIH grant AR53239. The authors thank Salvatore De Simone and Francesco D'Agnello for art graphics and the models in the figure. This work is dedicated to the memory of Eugenia Papa and Serafino Zappacosta.
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Matarese, G., Carrieri, P., Montella, S. et al. Leptin as a metabolic link to multiple sclerosis. Nat Rev Neurol 6, 455–461 (2010). https://doi.org/10.1038/nrneurol.2010.89
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DOI: https://doi.org/10.1038/nrneurol.2010.89
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