Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance
M. Carmen Navarro-Ruiz,
M. Carmen Soler-Vázquez,
Alberto Díaz-Ruiz,
Juan R. Peinado,
Andrea Nieto Calonge,
Julia Sánchez-Ceinos,
Carmen Tercero-Alcázar,
Jaime López-Alcalá,
Oriol A. Rangel-Zuñiga,
Antonio Membrives,
José López-Miranda,
María M. Malagón,
Rocío Guzmán-Ruiz
Affiliations
M. Carmen Navarro-Ruiz
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
M. Carmen Soler-Vázquez
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Alberto Díaz-Ruiz
Nutritional Interventions Group, Precision Nutrition and Aging, Madrid Institute for Advanced Studies—IMDEA Food, CEI UAM+CSIC, 28049 Madrid, Spain
Juan R. Peinado
Oxidative Stress and Neurodegeneration Group, Regional Center for Biomedical Research, Department of Medical Sciences, Ciudad Real Medical School, University of Castilla-La Mancha, 13001 Ciudad Real, Spain
Andrea Nieto Calonge
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Julia Sánchez-Ceinos
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Carmen Tercero-Alcázar
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Jaime López-Alcalá
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Oriol A. Rangel-Zuñiga
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
Antonio Membrives
General and Digestive Surgery Clinical Management Unit, Obesity Section, IMIBIC, Reina Sofía University Hospital, 14004 Córdoba, Spain
José López-Miranda
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
María M. Malagón
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Rocío Guzmán-Ruiz
Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
Background: Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress and metabolic dysfunction. The identification of specific carbonylated proteins in adipose tissue could provide novel biomarkers of oxidative damage related to metabolic status (i.e prediabetes). Thus, we aimed at characterizing the subcutaneous and omental human adipose tissue carbonylome in obesity-associated insulin resistance. Methods: 2D-PAGE was used to identify carbonylated proteins, and clinical correlations studies and molecular biology approaches including intracellular trafficking, reactive oxygen species assay, and iron content were performed using in vitro models of insulin resistance. Results: The carbonylome of human adipose tissue included common (serotransferrin, vimentin, actin, and annexin A2) and depot-specific (carbonic anhydrase and α-crystallin B in the subcutaneous depot; and α-1-antitrypsin and tubulin in the omental depot) differences that point out the complexity of oxidative stress at the metabolic level, highlighting changes in carbonylated transferrin expression. Posterior studies using in vitro prediabetic model evidence alteration in transferrin receptor translocation, linked to the prediabetic environment. Finally, ligand-receptor molecular docking studies showed a reduced affinity for carbonylated transferrin binding to its receptor compared to wild-type transferrin, emphasizing the role of transferrin carbonylation in the link between oxidative stress and metabolic dysfunction. Conclusions: The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance.
