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Serum irisin is upregulated in patients affected by amyotrophic lateral sclerosis and correlates with functional and metabolic status

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Abstract

Introduction

The progression of amyotrophic lateral sclerosis (ALS) leads to a decline of the nutritional status that represents an independent prognostic factor for survival. Recent studies recognize the muscle tissue as an endocrine organ able to release several molecules, called myokines. Among them, irisin seems to be involved in the regulation of metabolism, body weight and development and function of the nervous system.

Objectives

(1) To evaluate irisin serum levels in patients with ALS, with comparison to healthy subjects; (2) to assess the possible association of circulating irisin levels of ALS patients with the metabolic status, clinical and biochemical features.

Methods

We performed an observational, cross-sectional study in 50 ALS patients and 32 age- and sex-comparable healthy controls. Patients underwent to a complete set of neurological, pulmonary and nutritional evaluations. Serum irisin concentration was measured by enzyme immunoassay. According to indirect calorimetry, ALS patients were divided into a normo-metabolic patient group (n = 24) and a hyper-metabolic patient group (n = 26).

Results

ALS patients showed significantly higher serum irisin levels compared to healthy subjects (51.0 ± 37.8 vs 13.1 ± 2.2 ng/mL, p < 0.0001). Hyper-metabolic ALS patients displayed higher serum irisin levels compared to normo-metabolic ALS patients and healthy controls (p < 0.0009 and p < 0.0001, respectively). Serum irisin levels showed significant association with the ALSFRS-R (β=-1.18, p = 0.042), Forced Vital Capacity (β = − 0.64, p = 0.013), Fat Mass (β=-1.44, p = 0.034), pCO2 arterial blood levels (β = 2.67, p = 0.003), HCO3− arterial blood levels (β = 5.44, p = 0.001) and Free Fat Mass (β = 1.07, p = 0.025) adjusted for sex, age and metabolic status.

Conclusions

ALS patients with impaired metabolic status showed higher serum irisin levels compared to normo-metabolic ALS patients and healthy subjects. Irisin levels were also negatively correlated with the extent of functional and respiratory impairment, due to as yet unknown causes, being more elevated in patients with greater disability.

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Acknowledgements

We thank our patients and their caregivers for their support of our study.

Author information

Authors and Affiliations

  1. NEuroMuscular Omnicentre (NEMO), ASST Grande Ospedale Metropolitano Niguarda, Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy

    Christian Lunetta, Andrea Lizio & Valeria Sansone

  2. Neurology Unit, San Gerardo Hospital, ALS Clinic, University of Milano-Bicocca, Monza, Italy

    Lucio Tremolizzo

  3. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy

    Massimiliano Ruscica, Chiara Macchi & Paolo Magni

  4. Neuropathology Unit, Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy

    Nilo Riva

  5. Department of Neurology, Ulm University, Ulm, Germany

    Patrick Weydt

  6. Clinical Nutritional Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Ettore Corradi

  7. Department Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy

    Valeria Sansone

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  1. Christian Lunetta
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  2. Andrea Lizio
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Correspondence to Christian Lunetta.

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Conflicts of interest

The authors declare no financial support for the conduct of the study. Dr Lunetta served on a scientific advisory board for Neuraltus and Italfarmaco and has received funds from Agenzia Italiana per la Ricerca sulla SLA (ARISLA) and Ministry of Health (CCM2011). The other authors report no conflicts of interest.

Ethical standards

The study has been approved by our Ethics Committee. All data were gathered after informed consent was obtained from each participant, in accordance with specific national laws and the ethics standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Lunetta, C., Lizio, A., Tremolizzo, L. et al. Serum irisin is upregulated in patients affected by amyotrophic lateral sclerosis and correlates with functional and metabolic status. J Neurol 265, 3001–3008 (2018). https://doi.org/10.1007/s00415-018-9093-3

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  • DOI: https://doi.org/10.1007/s00415-018-9093-3

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