TY - JOUR
T1 - Immune-metabolic profiling of anorexic patients reveals an anti-oxidant and anti-inflammatory phenotype
AU - Omodei, Daniela
AU - Pucino, Valentina
AU - Labruna, Giuseppe
AU - Procaccini, Claudio
AU - Galgani, Mario
AU - Perna, Francesco
AU - Pirozzi, Daniele
AU - De Caprio, Carmela
AU - Marone, Gianni
AU - Fontana, Luigi
AU - Contaldo, Franco
AU - Pasanisi, Fabrizio
AU - Matarese, Giuseppe
AU - Sacchetti, Lucia
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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/m2) 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.
AB - 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/m2) 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.
KW - Anorexia nervosa
KW - Bioenergetics
KW - Immune-phenotype
KW - Oxidative stress
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U2 - 10.1016/j.metabol.2014.10.025
DO - 10.1016/j.metabol.2014.10.025
M3 - Article
C2 - 25500208
AN - SCOPUS:84921627781
VL - 64
SP - 396
EP - 405
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 3
ER -