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. 2022 Jul;67(7):3006-3016.
doi: 10.1007/s10620-021-07105-z. Epub 2021 Jun 22.

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

Cecilia C Garcia  1 , Bárbara Piotrkowski  2   3 , Plácida Baz  1 , Daniel Poncino  4 , Javier Benavides  5 , Luis Colombato  5 , María Laura Reyes Toso  6   7 , Silvina Yantorno  6   7 , Valeria Descalzi  6   7 , Gabriel E Gondolesi  6   7 , Cesar G Fraga  2   3 , Alejandra C Cherñavsky  8
Affiliations

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

Cecilia C Garcia et al. Dig Dis Sci. 2022 Jul.

Abstract

Background: Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of inflammation and redox homeostasis of different cell types. Increased resistin serum concentration 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 from NAFLD patients and controls.

Methods: We evaluated basal and resistin-mediated modulation of reactive oxygen species (ROS) and glutathione content by flow cytometry, and antioxidant enzyme activities by spectrophotometry.

Results: Peripheral blood mononuclear cells (PBMC) from NAFLD patients showed higher ROS content and glutathione peroxidase activity and lower glutathione content, superoxide dismutase and glutathione reductase activities than control PBMC. Resistin decreased ROS levels and superoxide dismutase activity and increased glutathione reductase and catalase activities in PBMC from controls but not from patients. Resistin decreased glutathione content in PBMC from control and NAFLD patients, with greater effect on patient cells. Basal and resistin-modulated ROS levels were directly associated with obesity-related risk factors for NAFLD. Hepatic myeloid cells and T-lymphocytes from NAFLD patients showed higher basal ROS content than cells from controls. Resistin decreased ROS levels in hepatic T-lymphocytes from controls but not from patients.

Conclusions: Resistin regulates redox homeostasis in mononuclear leukocytes. A decreased response to resistin in leukocytes from NAFLD patients is associated with an impaired redox homeostasis.

Keywords: Antioxidants; Fatty liver; Glutathione; Reactive oxygen species.

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