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

被引：29

作者：

Cimini, Flavia Agata ^{[1
]}

Arena, Andrea ^{[2
]}

Barchetta, Ilaria ^{[1
]}

Tramutola, Antonella ^{[2
]}

Ceccarelli, Valentina ^{[1
]}

Lanzillotta, Chiara ^{[2
]}

Fontana, Mario ^{[2
]}

Bertoccini, Laura ^{[1
]}

Leonetti, Frida ^{[1
]}

Capoccia, Danila ^{[1
]}

Silecchia, Gianfranco ^{[3
]}

Di Cristofano, Claudio ^{[3
]}

Chiappetta, Caterina ^{[3
]}

Di Domenico, Fabio ^{[2
]}

Baron, Marco Giorgio ^{[1
]}

Perluigi, Marzia ^{[2
]}

Cavallo, Maria Gisella ^{[1
]}

Barone, Eugenio ^{[2
]}

机构：

[1] Sapienza Univ Rome, Dept Expt Med, Rome, Italy

[2] Sapienza Univ Rome, Dept Biochem Sci A Rossi Fanelli, Piazzale A Moro 5, I-00185 Rome, Italy

[3] Sapienza Univ Rome, Dept Med Surg Sci & Biotechnol, Rome, Italy

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2019年 / 1865卷 / 06期

关键词：

Biliverdin reductase-a; Obesity; Insulin signaling; Metabolic disorders; BLOOD MONONUCLEAR-CELLS; SERUM BILIRUBIN LEVELS; NF-KAPPA-B; GENE-EXPRESSION; GLUCOSE DEPRIVATION; HEPATIC STEATOSIS; ALZHEIMER-DISEASE; HEME OXYGENASE; MESSENGER-RNA; UP-REGULATION;

D O I：

10.1016/j.bbadis.2019.02.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-313/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.

引用

页码：1490 / 1501

页数：12

共 70 条

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