Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice.
Basic Clin Pharmacol Toxicol
; 129(3): 173-182, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-34128319
ABSTRACT
Rosiglitazone has been reported to exert dual effects on liver steatosis, and it could exacerbate liver steatosis in obese animal models, which was suggested to be closely related to the elevated hepatic expression of FABP4. This study aimed to investigate whether combined treatment with FABP4 inhibitor I-9 could alleviate rosiglitazone-induced liver steatosis in obese diabetic db/db mice. Male C57BL/KsJ-db/db mice were orally treated with rosiglitazone, rosiglitazone combined with I-9 daily for 8 weeks. The liver steatosis was evaluated by triglyceride content and H&E staining. The expression of hepatic lipogenic genes or proteins in liver tissue or in FFA-treated hepatocytes and PMA-stimulated macrophages were determined by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. Results showed that combined treatment with I-9 decreased rosiglitazone-induced increase in serum FABP4 level and expression of lipogenic genes in liver, especially FABP4, and ameliorated liver steatosis in db/db mice. Rosiglitazone-induced intracellular TG accumulation and increased expression of FABP4 in the cultured hepatocytes and macrophages were also suppressed by combined treatment. We concluded that combined treatment with FABP4 inhibitor I-9 could ameliorate rosiglitazone-exacerbated elevated serum FABP4 level and ectopic liver fat accumulation in obese diabetic db/db mice without affecting its anti-diabetic efficacy.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a Ácido Graxo
/
Fígado Gorduroso
/
Rosiglitazona
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China