Premium
Combined treatment with FABP4 inhibitor ameliorates rosiglitazone‐induced liver steatosis in obese diabetic db/db mice
Author(s) -
Chen MengTing,
Huang JunShang,
Gao DingDing,
Li YingXia,
Wang HeYao
Publication year - 2021
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13621
Subject(s) - rosiglitazone , steatosis , medicine , endocrinology , triglyceride , fatty liver , diabetes mellitus , oil red o , adipogenesis , adipose tissue , cholesterol , disease
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.