Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes

doi:10.1007/s12020-019-02157-8

	Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes
	Dou, Hui-Xia 1,2; Wang, Ting 1; Su, Hai-Xia 1,2; Gao, Ding-Ding 3; Xu, Ye-Chun 1; Li, Ying-Xia 3; Wang, He-Yao 1,2
刊名	ENDOCRINE
	2020-03-01
卷号	67 期号:3 页码:587-596
关键词	eFABP4 Adipocyte Differentiation Lipolysis Inflammation
ISSN号	1355-008X
DOI	10.1007/s12020-019-02157-8
通讯作者	Wang, He-Yao(hywang@simm.ac.cn)
英文摘要	Purpose Fatty acid binding protein 4 (FABP4) has been demonstrated to be secreted from adipocytes in an unconventional pathway associated with lipolysis. Circulating FABP4 is elevated in metabolic disorders and has been shown to affect various peripheral cells such as pancreatic beta-cells, hepatocytes and macrophages, but its effects on adipocytes remains unclear. The aim of this study was to investigate the effects of exogenous FABP4 (eFABP4) on adipocyte differentiation and function. Methods 3T3-L1 pre-adipocytes or mature adipocytes were treated with recombinant FABP4 in the absence or presence of FABP4 inhibitor I-9/p38 MAPK inhibitor SB203580; Meanwhile male C57BL/6J mice were subcutaneously injected twice a day with recombinant FABP4 (0.35 mg/kg) with or without I-9 (50 mg/kg) for 2 weeks. The effects of eFABP4 on differentiation, lipolysis and inflammation were determined by triglyceride measurement or lipolysis assay, western blotting, or RT-qPCR analysis. Results eFABP4 treatment significantly reduced intracellular triglyceride content and decreased expression of adipogenic markers peroxisome proliferator-activated receptor gamma (PPAR gamma), CCAAT/enhancer binding protein alpha (C/EBP alpha), intracellular FABP4, and adiponectin in 3T3-L1 cells. Besides, eFABP4 promoted lipolysis and inflammation in differentiated 3T3-L1 adipocytes as well as in adipose tissue of eFABP4-treated C57BL/6J mice, with elevated gene expression of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-alpha, and elevated protein expression of adipose triglyceride lipase (ATGL), phosphorylation of hormone-sensitive lipase (HSL) (Ser-660), p38, and nuclear factor-kappa B (NF-kappa B). The pro-inflammatory and pro-lipolytic effects of eFABP4 could be reversed by SB203580/I-9. Conclusions These findings indicate that eFABP4 interferes with adipocyte differentiation, induces p38/HSL mediated lipolysis and p38/NF-kappa B mediated inflammation in adipocytes in vitro and in vivo.
WOS关键词	ACID-BINDING PROTEIN ; ENDOPLASMIC-RETICULUM STRESS ; NF-KAPPA-B ; ADIPOSE-TISSUE ; IMPAIRED ADIPOGENESIS ; INSULIN-SECRETION ; CYTOKERATIN 1 ; PPAR-GAMMA ; OBESITY ; BIOMARKER
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000518803900010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281134]
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, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Dou, Hui-Xia,Wang, Ting,Su, Hai-Xia,et al. Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes[J]. ENDOCRINE,2020,67(3):587-596.
APA	Dou, Hui-Xia.,Wang, Ting.,Su, Hai-Xia.,Gao, Ding-Ding.,Xu, Ye-Chun.,...&Wang, He-Yao.(2020).Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes.ENDOCRINE,67(3),587-596.
MLA	Dou, Hui-Xia,et al."Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes".ENDOCRINE 67.3(2020):587-596.