Vol.:(0123456789) 1 3 Journal of Neurology https://doi.org/10.1007/s00415-018-9093-3 ORIGINAL COMMUNICATION Serum irisin is upregulated in patients affected by amyotrophic lateral sclerosis and correlates with functional and metabolic status Christian Lunetta 1  · Andrea Lizio 1  · Lucio Tremolizzo 2  · Massimiliano Ruscica 3  · Chiara Macchi 3  · Nilo Riva 4  · Patrick Weydt 5  · Ettore Corradi 6  · Paolo Magni 3  · Valeria Sansone 1,7 Received: 25 June 2018 / Revised: 9 October 2018 / Accepted: 10 October 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Introduction The progression of amyotrophic lateral sclerosis (ALS) leads to a decline of the nutritional status that repre- sents 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 con- centration 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), pCO 2 arterial blood levels (β = 2.67, p = 0.003), HCO 3 − 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. Keywords ALS · Irisin · Metabolism · Myokine · Serum * Christian Lunetta christian.lunetta@centrocliniconemo.it 1 NEuroMuscular Omnicentre (NEMO), ASST Grande Ospedale Metropolitano Niguarda, Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy 2 Neurology Unit, San Gerardo Hospital, ALS Clinic, University of Milano-Bicocca, Monza, Italy 3 Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy 4 Neuropathology Unit, Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy 5 Department of Neurology, Ulm University, Ulm, Germany 6 Clinical Nutritional Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy 7 Department Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy