Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice

doi:10.1111/bcpt.13621

	Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice
	Chen, Meng-Ting 1,2; Huang, Jun-Shang 1,2; Gao, Ding-Ding 3; Li, Ying-Xia 3; Wang, He-Yao 1,2
刊名	BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
	2021-06-15
页码	10
关键词	combined treatment FABP4 inhibitor liver steatosis obese type 2 diabetes rosiglitazone
ISSN号	1742-7835
DOI	10.1111/bcpt.13621
通讯作者	Wang, He-Yao(hywang@simm.ac.cn)
英文摘要	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.
资助项目	Ministry of Science and Technology of the People's Republic of China[2018ZX09711002-002-007] ; Chinese Academy of Sciences[XDA12040336] ; National Natural Science Foundation of China[81473262] ; National Natural Science Foundation of China[81773791]
WOS关键词	ACID-BINDING PROTEIN ; PPAR-GAMMA ; PEROXISOME PROLIFERATOR ; GENE-EXPRESSION ; FATTY LIVER ; NONALCOHOLIC STEATOHEPATITIS ; INSULIN-RESISTANCE ; HEPATIC STEATOSIS ; LIPID-METABOLISM ; GLUCOSE
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	WILEY
WOS记录号	WOS:000661668000001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297140]
专题	中国科学院上海药物研究所
通讯作者	Wang, He-Yao
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China 3.Fudan Univ, Sch Pharm, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Chen, Meng-Ting,Huang, Jun-Shang,Gao, Ding-Ding,et al. Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice[J]. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,2021:10.
APA	Chen, Meng-Ting,Huang, Jun-Shang,Gao, Ding-Ding,Li, Ying-Xia,&Wang, He-Yao.(2021).Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice.BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,10.
MLA	Chen, Meng-Ting,et al."Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice".BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY (2021):10.