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Leptin as a metabolic link to multiple sclerosis

Nature Reviews Neurology volume 6, pages 455–461 (2010)Cite this article

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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

  • Leptin is an adipocyte-derived hormone that is secreted proportionally to adipose tissue mass and inhibits food intake

  • Leptin links the immune response to metabolism and nutritional status

  • Leptin promotes proinflammatory immune responses and inhibits the proliferation of anti-inflammatory regulatory T cells

  • Orexigenic mediators antagonize the anorexigenic and proinflammatory effects of leptin in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS)

  • Drugs that affect metabolism are effective at reducing the proinflammatory effects of leptin in EAE

  • 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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Figure 1: Intracellular leptin signaling in immune cells.
Figure 2: Immune function and metabolic status.

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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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Authors and Affiliations

  1. Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Via S. Pansini 5, Napoli, 80131, Italy

    Giuseppe Matarese & Veronica De Rosa

  2. Dipartimento di Scienze Neurologiche, Università di Napoli “Federico II”, Via S. Pansini 5, Napoli, 80131, Italy

    Pietro Biagio Carrieri & Silvana Montella

  3. Department of Medicine, University of California Los Angeles, 1000 Veteran Avenue, Los Angeles, 90095, CA, USA

    Antonio La Cava

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  1. Giuseppe Matarese
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Correspondence to Giuseppe Matarese.

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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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