Comprehensive metabolomic characterization of whole-body PIGR deletion in serum, liver and visceral white adipose tissue by GC-MS

Ferrarini A., ERTEKİN ÖZKAN Z. C., Picatoste B., Cerro Pardo I., Martin-Ventura J. L., Vázquez J.

2nd International Conference of the Spanish Society of Metabolomics (SESMet 2024), Sevilla, İspanya, 03 Haziran 2024, ss.27-28

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Sevilla
  • Basıldığı Ülke: İspanya
  • Sayfa Sayıları: ss.27-28
  • Ankara Üniversitesi Adresli: Evet

Özet

Obesity represents the leading cause of several noncommunicable diseases, including type 2 diabetes mellitus (T2DM). In fact, the associated risk of developing T2DM in overweighed individuals is enormously high. Nevertheless, the mechanisms at the basis of this relationship are far from being understood and rely on complex interplays between glucose homeostasis, inflammation and autoimmunity.

Polymeric immunoglobulin receptor (pIgR) plays a central role in mucosal immunity by facilitating IgA translocation across epithelial barriers during the immune response. High fat diet (HFD) is well-known to trigger several immunogenic events and has been associated to altered IgA frequency and production in mice. Furthermore, HFD-fed-IgA-deficient mice show exacerbated adipose tissue inflammation and disrupted glucose and host-microbiome homeostasis, suggesting a possible involvement of pIgR in obesity-induced insulin resistance (IR).

In order to understand the role of pIgR and IgA during the onset of T2DM, we applied GC-MS-based untargeted metabolomics to characterized metabolites alterations in serum, liver and visceral white adipose tissue (vWAT) in the pIgR−/− murine model of obesity-induced IR.

Following metabolite extraction, supernatant was dried-out and submitted to a two-step derivatization process consisting of methoximation and sylilation. The amount of reagents and sample was optimized to achieved the best recovery. Samples were analyzed using an 8890 Agilent GC-system coupled to the LECO Pegasus BT-TOF-MS. Data processing, including deconvolution, alignment and metabolites identification were performed using LECO ChromaTOFSync. Low analytical variability was confirmed through quality assurance, with statistical analysis revealing significant differences in carbohydrates, fatty acids, nucleic acids

and organic acids across serum, liver, and vWAT.

The identified alterations could serve as pivotal indicators, shedding light on the complex mechanisms underlying T2DM onset in an obesogenic environment. This study underscores the importance of PIgR and IgA in modulating metabolic processes and highlights the potential of metabolomics in elucidating disease pathogenesis and identifying therapeutic targets.