气候变化领域集成服务门户(CCPortal): TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells

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DOI	10.21037/atm-21-4012
	TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells
	Zhang, Liting; Xie, Zehui; Yu, Hongmiao; Du, Haoxuan; Wang, Xuqiao; Cai, Jiazheng; Qiu, Yingfei; Chen, Rui; Jiang, Xiaofeng; Liu, Zelin; Li, Yi; Chen, Tuo
通讯作者	Li, Y ; Chen, T (通讯作者)，Chinese Acad Sci, Northwest Inst Ecoenvironm & Resources, State Key Lab Cryospher Sci, Lanzhou 730000, Peoples R China. ; Chen, T (通讯作者)，Univ Chinese Acad Sci, Beijing 100049, Peoples R China. ; Li, Y (通讯作者)，Lanzhou Univ, Sch Stomatol, Lanzhou 730000, Peoples R China.
发表日期	2021
ISSN	2305-5839
EISSN	2305-5847
卷号	9 期号:18
英文摘要	Background: Gut microbiome dysbiosis is related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), and the role of toll-like receptor 2 (TLR2) in its molecular mechanism is controversial. Here, we investigated the effects and mechanisms of Escherichia coli-derived lipopolysaccharide (LPS) on lipid accumulation and lipotoxicity in palmitic acid (PA)-treated L02 cell as an NAFLD cell model, and the role of TLR2 in this process. Methods: Oil red O staining assay and free fatty acid (FFA) content test were performed to determine the effects of LPS on lipid accumulation in a PA-induced NAFLD cell model with or without TLR2 inhibition. The levels of IL-6 and TNF-alpha were measured to investigate inflammation conditions. Hoechst 33342 staining assay and Caspase-3 activity assay were used to test cell apoptosis, and the expression levels of proteins in the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKK alpha/NF-kappa B signaling pathway, and mitochondrion-dependent apoptotic signaling pathway were detected using Western blot. Results: Lipid accumulation, pro-inflammatory cytokine release, and cell apoptosis with high levels were observed in the PA-induced NAFLD cell model, and LPS aggravated these processes. Whereas TLR2 inhibition could significantly ameliorate PA-induced and LPS-amplified lipid accumulation, inflammatory, and cell apoptosis, it had no significant effect on L02 cells treated with LPS alone. Conclusions: These results were confirmed by activation or inhibition of the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKK alpha/NF-kappa B signaling pathway, and mitochondrion-dependent apoptotic signaling pathway, and were reflected by changes on their proteins expression. TLR2 is involved in PA-induced lipid accumulation and lipotoxicity in L02 cells, which could be aggravated by LPS, although LPS-induced amplification might not be through direct interaction with TLR2.
关键词	FATTY LIVER-DISEASE NONALCOHOLIC STEATOHEPATITIS ADVANCED FIBROSIS LIPOPOLYSACCHARIDE RECEPTORS AXIS ACID
英文关键词	Toll-like receptor 2; lipopolysaccharide (LPS); nonalcoholic fatty liver disease (NAFLD); lipid accumulation; inflammation
语种	英语
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS类目	Oncology ; Medicine, Research & Experimental
WOS记录号	WOS:000707156200011
来源期刊	ANNALS OF TRANSLATIONAL MEDICINE
来源机构	中国科学院西北生态环境资源研究院
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/254514
作者单位	[Zhang, Liting; Li, Yi; Chen, Tuo] Chinese Acad Sci, Northwest Inst Ecoenvironm & Resources, State Key Lab Cryospher Sci, Lanzhou 730000, Peoples R China; [Zhang, Liting; Chen, Tuo] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [Zhang, Liting] Lanzhou Univ, Hosp 1, Dept Infect Dis, Lanzhou, Peoples R China; [Xie, Zehui] Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China; [Yu, Hongmiao] Fudan Univ, Childrens Hosp, Shanghai, Peoples R China; [Yu, Hongmiao] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China; [Du, Haoxuan] Lanzhou Univ, Clin Med Coll 1, Lanzhou, Peoples R China; [Wang, Xuqiao; Cai, Jiazheng; Qiu, Yingfei; Chen, Rui; Jiang, Xiaofeng; Liu, Zelin; Li, Yi] Lanzhou Univ, Sch Hosp Stomatol, Lanzhou, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Liting,Xie, Zehui,Yu, Hongmiao,et al. TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells[J]. 中国科学院西北生态环境资源研究院,2021,9(18).
APA	Zhang, Liting.,Xie, Zehui.,Yu, Hongmiao.,Du, Haoxuan.,Wang, Xuqiao.,...&Chen, Tuo.(2021).TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells.ANNALS OF TRANSLATIONAL MEDICINE,9(18).
MLA	Zhang, Liting,et al."TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells".ANNALS OF TRANSLATIONAL MEDICINE 9.18(2021).