Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity.
Biochim Biophys Acta Mol Basis Dis
; 1865(6): 1490-1501, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-30826467
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-3ß/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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Transdução de Sinais
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Regulação da Expressão Gênica
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Oxirredutases atuantes sobre Doadores de Grupo CH-CH
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Insulina
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Obesidade
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália