2. Academic Validation
  3. Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity

Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity

  • Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1490-1501. doi: 10.1016/j.bbadis.2019.02.021.
Flavia Agata Cimini 1,  Andrea Arena 2,  Ilaria Barchetta 1,  Antonella Tramutola 2,  Valentina Ceccarelli 1,  Chiara Lanzillotta 2,  Mario Fontana 2,  Laura Bertoccini 1,  Frida Leonetti 1,  Danila Capoccia 1,  Gianfranco Silecchia 3,  Claudio Di Cristofano 3,  Caterina Chiappetta 3,  Fabio Di Domenico 2,  Marco Giorgio Baroni 1,  Marzia Perluigi 2,  Maria Gisella Cavallo 4,  Eugenio Barone 5
Affiliations

Affiliations

  • 1 Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
  • 2 Department of Biochemical Sciences "A. Rossi-Fanelli" Sapienza University of Rome, Rome, Italy.
  • 3 Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Rome, Italy.
  • 4 Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
  • 5 Department of Biochemical Sciences "A. Rossi-Fanelli" Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
PMID: 30826467 DOI: 10.1016/j.bbadis.2019.02.021
Abstract

Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of Insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the Insulin Receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/Insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the Insulin along with clinical correlates. We showed that BVR-A levels are significantly reduced in obese subjects and associated with a hyper-activation of the IR/IRS1/Akt/GSK-3β/AS160/GLUT4 pathway. Low BVR-A levels also associate with the presence of obesity, metabolic syndrome, NASH and visceral adipose tissue inflammation. These data suggest that the reduction of BVR-A may be responsible for early alterations of the Insulin signaling pathway in obesity and in this context may represent a novel molecular target to be investigated for the comprehension of the process of Insulin resistance development in obesity.

Keywords

Biliverdin reductase-a; Insulin signaling; Metabolic disorders; Obesity.

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