Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis

doi:10.1186/s12944-019-1118-0

	Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis
	Yang, Rui-Xu 3; Pan, Qin 3; Liu, Xiao-Lin 3; Zhou, Da 3; Xin, Feng-Zhi 3; Zhao, Ze-Hua 3; Zhang, Rui-Nan 3; Zeng, Jing 3; Qiao, Liang 4; Hu, Chun-Xiu 1
刊名	LIPIDS IN HEALTH AND DISEASE
	2019-10-21
卷号	18 期号:1 页码:11
关键词	Ceramides Autophagy High fat diet Non-alcoholic fatty liver disease
DOI	10.1186/s12944-019-1118-0
通讯作者	Fan, Jian-Gao(fanjiangao@xinhuamed.com.cn)
英文摘要	Background Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. Methods Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB). Results Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Ppar alpha, Cpt-1 alpha and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB. Conclusions Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH.
资助项目	National Key Research and Development Plan 'Precision Medicine Research'[2017YFSF090203] ; National Natural Science Foundation of China[81873565] ; National Natural Science Foundation of China[81900507]
WOS关键词	INSULIN-RESISTANCE ; LIVER-DISEASE ; CERAMIDE ; INHIBITION ; SPHINGOLIPIDS ; STEATOSIS ; OXIDATION ; PARADOX
WOS研究方向	Biochemistry & Molecular Biology ; Nutrition & Dietetics
语种	英语
出版者	BMC
WOS记录号	WOS:000491351200001
资助机构	National Key Research and Development Plan 'Precision Medicine Research' ; National Key Research and Development Plan 'Precision Medicine Research' ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Plan 'Precision Medicine Research' ; National Key Research and Development Plan 'Precision Medicine Research' ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Plan 'Precision Medicine Research' ; National Key Research and Development Plan 'Precision Medicine Research' ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Plan 'Precision Medicine Research' ; National Key Research and Development Plan 'Precision Medicine Research' ; National Natural Science Foundation of China ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/172403]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Fan, Jian-Gao
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China 2.Shanghai Key Lab Pediat Gastroenterol & Nutr, Shanghai 200092, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Ctr Fatty Liver,Dept Gastroenterol, Shanghai 200092, Peoples R China 4.Univ Sydney, Westmead Hosp, Westmead Inst Med Res, Storr Liver Ctr, Westmead, NSW 2145, Australia
推荐引用方式 GB/T 7714	Yang, Rui-Xu,Pan, Qin,Liu, Xiao-Lin,et al. Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis[J]. LIPIDS IN HEALTH AND DISEASE,2019,18(1):11.
APA	Yang, Rui-Xu.,Pan, Qin.,Liu, Xiao-Lin.,Zhou, Da.,Xin, Feng-Zhi.,...&Fan, Jian-Gao.(2019).Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis.LIPIDS IN HEALTH AND DISEASE,18(1),11.
MLA	Yang, Rui-Xu,et al."Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis".LIPIDS IN HEALTH AND DISEASE 18.1(2019):11.