A Decreased Response to Resistin in Mononuclear Leukocytes Contributes to Oxidative Stress in Nonalcoholic Fatty Liver Disease

BAZ PLACIDA; COLOMBATO LUIS; DESCALZI VALERIA; CHERÑAVSKY ALEJANDRA CLAUDIA; PIOTROWSKY BARBARA; CECILIA GARCIA; BENAVIDEZ JAVIER; PONCINO DANIEL; YANTORNO SILVINA; REYES TOSO MARÍA LAURA; FRAGA CÉSAR; GONDOLESI GABRIEL

DIGESTIVE DISEASE AND SCIENCES

Springer

Lugar: Los Angeles; Año: 2021

0163-2116

both deregulation of immune response and oxidative stress contribute toNon-alcoholic fatty liver disease (NAFLD) pathogenesis. In different cell types, resistin acts as a physiological modulator of inflammation and redox homeostasis. Increased resistin serum levels and the direct association between resistin hepatic expression and NAFLD severity suggest that resistin participates in NAFLD pathogenesis. Aims: to evaluate resistin-induced regulation of redox homeostasis in mononuclear leukocytes. Methods : we evaluated basal and resistin-mediated modulation of reactive oxygen species (ROS) and glutathione content by flow cytometry, and basal and resistin-mediated modulation of antioxidant enzymatic activities in circulating and liver-infiltrating mononuclear leukocytes from NAFLD patients and controls.Results : circulating leukocytes from NAFLD patients showed higher ROS content and glutathione peroxidase activity, but lower glutathione content, superoxide dismutase and glutathione reductase activities. Resistin induced a decrease of ROS levels and superoxide dismutase activity, and an increase of glutathione reductase and catalase activity in circulating leukocytes from controls but not from patients. Resistin decreased glutathione content in circulating leukocytes from controls and NAFLD patients, with a greater effect on patients. Basal and resistin-modulated ROS levels were directly associated with obesity-related risk factors for NAFLD. Liver-infiltrating macrophages and T-lymphocytes from NAFLD patients showed higher basal ROS content. Resistin induced a decrease in ROS levels in liver-infiltrating T-lymphocytes from controls, but not from patients. Conclusions : resistin is involved in the regulation of redoxhomeostasis in mononuclear leukocytes. A decreased response to resistin in leukocytes from NAFLD patients is associated with a shift in redox homeostasis