(5R)-5-hydroxytriptolide ameliorates liver lipid accumulation by suppressing lipid synthesis and promoting lipid oxidation in mice

doi:10.1016/j.lfs.2019.116644

	(5R)-5-hydroxytriptolide ameliorates liver lipid accumulation by suppressing lipid synthesis and promoting lipid oxidation in mice
	Dong, Yunxia 1,3; Lu, Henglei 1,2; Li, Qiang 1; Qi, Xinming 1; Li, Yuanchao 1; Zhang, Zean 2; Chen, Jing 1,3; Ren, Jin 1,3
刊名	LIFE SCIENCES
	2019-09-01
卷号	232 页码:9
关键词	(5R)-5-hydroxytriptolide NAFLD Lipid synthesis Fatty acids oxidation Fat deposition
ISSN号	0024-3205
DOI	10.1016/j.lfs.2019.116644
通讯作者	Chen, Jing(jingchen@simm.ac.cn) ; Ren, Jin(jren@cdser.simm.ac.cn)
英文摘要	Aims: (5R)-5-hydroxytriptolide (LLDT-8) is a triptolide analog with excellent capability against cancers, cerebral ischemic injury and rheumatoid arthritis. Here, we discovered its hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease (NAFLD) by ameliorating liver lipid accumulation. Main methods: Male C57BL/6J mice were fed with a high-fat/high-fructose (HFHFr) diet for 29 weeks to induce the pathological phenomena of NAFLD. Then the mice were treated with LLDT-8 (0.5mg/kg and 1 mg/kg) or Vehicle for 8 weeks. Finally, the serum biochemical indexes, liver histological features, fatty acids (FAs) profile and related gene expression in liver were detected to investigate the effect of LLDT-8 on lipid accumulation and its possible mechanism. Key findings: LLDT-8 treatment significantly inhibited hepatic injury featured by the decrease of serum alanine aminotransferase (ALT) and aspartate transaminase (AST), the lessening of hepatic ballooning and macro-vesicular steatosis. Moreover, LLDT-8 could downregulate the expression of stearoyl-CoA desaturase 1 (SCD1), which further led to the lower ratios of C16:1/C16:0 and C18:1/C18:0 and thus inhibited lipid synthesis. LLDT-8 treatment also could upregulate liver peroxisome proliferator-activated receptor alpha (PPAR alpha), carnitine palmitoyltransferase 1a (Cpt1a), peroxisomal acyl-CoA oxidase 1 (Acox1), long-chain acyl-CoA dehydrogenase (Acadl) and medium-chain acyl-CoA dehydrogenase (Acadm) expression levels involved in fatty acids oxidation (FAO) and markedly promoted lipolysis. Significance: Our results provide a novel application of LLDT-8 in improving NAFLD.
资助项目	National Natural Science Foundation of China[81870401]
WOS关键词	ACTIVATED RECEPTOR-ALPHA ; FATTY-ACID-METABOLISM ; NONALCOHOLIC STEATOHEPATITIS ; INSULIN-RESISTANCE ; HEPATIC STEATOSIS ; TRIPTOLIDE ; DISEASE ; MITOCHONDRIAL ; TOXICITY
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000481623100002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288898]
专题	中国科学院上海药物研究所
通讯作者	Chen, Jing; Ren, Jin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Safety Evaluat & Res, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Dong, Yunxia,Lu, Henglei,Li, Qiang,et al. (5R)-5-hydroxytriptolide ameliorates liver lipid accumulation by suppressing lipid synthesis and promoting lipid oxidation in mice[J]. LIFE SCIENCES,2019,232:9.
APA	Dong, Yunxia.,Lu, Henglei.,Li, Qiang.,Qi, Xinming.,Li, Yuanchao.,...&Ren, Jin.(2019).(5R)-5-hydroxytriptolide ameliorates liver lipid accumulation by suppressing lipid synthesis and promoting lipid oxidation in mice.LIFE SCIENCES,232,9.
MLA	Dong, Yunxia,et al."(5R)-5-hydroxytriptolide ameliorates liver lipid accumulation by suppressing lipid synthesis and promoting lipid oxidation in mice".LIFE SCIENCES 232(2019):9.