Daniela Omodei1, Valentina Pucino2, Giuseppe Labruna3, Claudio Procaccini4, Mario Galgani4, Francesco Perna5, Daniele Pirozzi6, Carmela De Caprio7, Gianni Marone2, Luigi Fontana8, Franco Contaldo7, Fabrizio Pasanisi7, Giuseppe Matarese9, Lucia Sacchetti10. 1. CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy. 2. Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. 3. IRCCS Fondazione SDN, Istituto di Ricerca Diagnostica e Nucleare, 80143 Naples, Italy. 4. 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. 5. Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. 6. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. 7. Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy. 8. 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. 9. Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, 84081 Salerno, Italy & IRCCS-MultiMedica, 20138 Milano, Italy. 10. 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.
Abstract
CONTEXT: 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. OBJECTIVES: 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. DESIGN: 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.
CONTEXT: 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. OBJECTIVES: 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. DESIGN: 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.
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