DICP OpenIR
Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis
Yang, Rui-Xu1; Pan, Qin1; Liu, Xiao-Lin1; Zhou, Da1; Xin, Feng-Zhi1; Zhao, Ze-Hua1; Zhang, Rui-Nan1; Zeng, Jing1; Qiao, Liang2; Hu, Chun-Xiu3; Xu, Guo-Wang3; Fan, Jian-Gao1,4
Corresponding AuthorFan, Jian-Gao(fanjiangao@xinhuamed.com.cn)
KeywordCeramides Autophagy High fat diet Non-alcoholic fatty liver disease
Source PublicationLIPIDS IN HEALTH AND DISEASE
2019-10-21
DOI10.1186/s12944-019-1118-0
Volume18Issue:1Pages:11
Funding ProjectNational Key Research and Development Plan 'Precision Medicine Research'[2017YFSF090203] ; National Natural Science Foundation of China[81873565] ; National Natural Science Foundation of China[81900507]
Funding OrganizationNational 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
WOS SubjectBiochemistry & Molecular Biology ; Nutrition & Dietetics
WOS Research AreaBiochemistry & Molecular Biology ; Nutrition & Dietetics
WOS KeywordINSULIN-RESISTANCE ; LIVER-DISEASE ; CERAMIDE ; INHIBITION ; SPHINGOLIPIDS ; STEATOSIS ; OXIDATION ; PARADOX
AbstractBackground 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.
Language英语
Funding OrganizationNational 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
WOS IDWOS:000491351200001
PublisherBMC
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/172404
Collection中国科学院大连化学物理研究所
Corresponding AuthorFan, Jian-Gao
Affiliation1.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Ctr Fatty Liver,Dept Gastroenterol, Shanghai 200092, Peoples R China
2.Univ Sydney, Westmead Hosp, Westmead Inst Med Res, Storr Liver Ctr, Westmead, NSW 2145, Australia
3.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
4.Shanghai Key Lab Pediat Gastroenterol & Nutr, Shanghai 200092, Peoples R China
Recommended Citation
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.
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