LXR activation by GW3965 alters fat tissue distribution and adipose tissue inflammation in ob/ob female mice.
J Lipid Res
; 54(5): 1300-11, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23446231
ABSTRACT
To investigate the role of liver X receptor (LXR) in adipose tissue metabolism during obesity, ob/ob mice were treated for 5 weeks with the synthetic LXR agonist GW3965. MRI analysis revealed that pharmacological activation of LXR modified fat distribution by decreasing visceral (VS) fat and inversely increasing subcutaneous (SC) fat storage without affecting whole body fat content. This was concordant with opposite regulation by GW3965 of the lipolytic markers hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in the two fat depots; moreover, the expression of genes involved in lipogenesis was significantly induced in SC fat. Lipidomic analysis suggested that changes in lipid composition in response to GW3965 also varied between VS and SC fat. In both depots, the observed alteration in lipid composition indicated an overall change toward less lipotoxic lipids. Flow cytometry analysis showed decreased immune cell infiltration in adipose tissue of ob/ob mice in response to GW3965 treatment, which in VS fat mainly affected the macrophage population and in SC fat the lymphocyte population. In line with this, the expression and secretion of proinflammatory markers was decreased in both fat deposits with GW3965 treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzoatos
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Benzilaminas
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Tecido Adiposo
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Receptores Nucleares Órfãos
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Obesidade
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos