Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways.
Prostaglandins Other Lipid Mediat
; 173: 106840, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38830399
ABSTRACT
We have previously demonstrated that the glucocorticoid receptor ß (GRß) isoform induces hepatic steatosis in mice fed a normal chow diet. The GRß isoform inhibits the glucocorticoid-binding isoform GRα, reducing responsiveness and inducing glucocorticoid resistance. We hypothesized that GRß regulates lipids that cause metabolic dysfunction. To determine the effect of GRß on hepatic lipid classes and molecular species, we overexpressed GRß (GRß-Ad) and vector (Vec-Ad) using adenovirus delivery, as we previously described. We fed the mice a normal chow diet for 5 days and harvested the livers. We utilized liquid chromatography-mass spectrometry (LC-MS) analyses of the livers to determine the lipid species driven by GRß. The most significant changes in the lipidome were monoacylglycerides and cholesterol esters. There was also increased gene expression in the GRß-Ad mice for lipogenesis, eicosanoid synthesis, and inflammatory pathways. These indicate that GRß-induced glucocorticoid resistance may drive hepatic fat accumulation, providing new therapeutic advantages.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Receptores de Glucocorticoides
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Eicosanoides
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Lipogénesis
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Glucocorticoides
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Inflamación
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Hígado
Límite:
Animals
Idioma:
En
Revista:
Prostaglandins & other lipid mediators
/
Prostaglandins Other Lipid Mediat
/
Prostaglandins other lipid mediat
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos