title: Immune-metabolic profiling of anorexic patients reveals an anti-oxidant and anti-inflammatory phenotype.
abstract: BACKGROUND
  Anorexia nervosa (AN) is an excessive form of calorie restriction (CR) associated with pathological weight loss and alterations of the immune system. However, AN patients seem to be protected from common viral infections.
  
  
  OBJECTIVE
  To investigate the metabolic and molecular adaptations induced by sustained extreme CR in the peripheral blood mononuclear cells (PBMCs) of patients with restrictive alimentary AN.
  
  
  METHODS
  Inflammatory cytokines and adipokines were measured in 15 young (age range, 15-24 years) AN female patients and 20 age-matched healthy controls. Isolated PBMCs were immunophenotyped by flow cytometry, and glycolysis and mitochondrial respiration were determined by measuring the extracellular acidification and oxygen consumption rate. Stress resistance to H2O2 and the antioxidant transcriptional profile of PBMCs and human fibroblasts incubated with sera from AN patients were also determined.
  
  
  RESULTS
  Compared with controls, AN patients (BMI, 15.9±0.4 kg/m(2)) had significantly fewer leucocytes, lymphocytes and NK cells, lower serum concentrations of leptin, IGF-1 and sTNFR1, and higher levels of adiponectin, sCD40L and sICAM-1 (p<0.05). IL-1β, TNFα, and IL-6 produced by PBMC cultured with autologous serum for 48 h were significantly lower in AN patients than in controls (p<0.01). Moreover, glycolysis and mitochondrial respiration were lower, and the antioxidant transcriptional profile was higher in the PBMCs of AN patients. Fibroblasts cultured in serum from AN patients showed a 24% increase in resistance to H2O2 damage.
  
  
  CONCLUSIONS
  Extreme CR in AN patients is associated with a reduction in several immune cell populations, but with higher antioxidant potential, stress resistance and an anti-inflammatory status.
authors.affiliation: CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Omodei
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pucino
authors.affiliation: IRCCS Fondazione SDN, Istituto di Ricerca Diagnostica e Nucleare, 80143 Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Labruna
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Procaccini
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Galgani
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perna
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pirozzi
authors.affiliation: Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: De Caprio
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Marone
authors.affiliation: CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy; Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, 25123 Brescia, Italy; Division of Geriatrics and Nutritional Science, Washington University, St. Louis, MO, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.affiliation: Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Contaldo
authors.affiliation: Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pasanisi
authors.affiliation: Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, 84081 Salerno, Italy & IRCCS-MultiMedica, 20138 Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.affiliation: CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. Electronic address: sacchett@unina.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000276:immunology* / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D018384:Oxidative Stress; D010101:Oxygen Consumption; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D054392:Adipokines; D000975:Antioxidants; D016207:Cytokines
keywords: Anorexia nervosa; Bioenergetics; Immune-phenotype; Oxidative stress