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Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy
Liu, Jingxin1,2,3; Zhang, Tian2,4; Zhu, Jianzhong2; Ruan, Shuangchen1; Li, Rongsong3; Guo, Bing4; Lin, Ligen2
2021-12-01
Source PublicationChinese Medicine
ISSN1749-8546
Volume16Issue:1
Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic accumulation of triglycerides in the liver. Emerging evidence has demonstrated that lipophagy regulates lipid mobilization and energy homeostasis in the liver. Sirtuin 3 (SIRT3), a mitochondrial NAD-dependent deacetylase, modulates the activities of several substrates involving in autophagy and energy metabolism. Honokiol (HK) is a natural lignan from the plants of Magnolia genus that exhibits potent liver protective property. Methods: AML12 was challenged with 500 μM palmitic acid and 250 μM oleic acid mixture solution to induce lipotoxicity. C57BL/6J mice were fed with a choline-deficient high fat diet (CDHFD) to generate liver steatosis. The expression of autophagy-related and AMP-activated protein kinase (AMPK) pathway proteins was evaluated by Western blotting and immunofluorescence staining. Intracellular lipid accumulation was validated by Nile red staining. Molecular docking analysis was performed on AutoDock 4.2. Results: HK (5 and 10 μM) was found to attenuate lipid accumulation through promoting SIRT3-AMPK-mediated autophagy, mainly on lipid droplets. HK had hydrophobic interaction with amino acid residues (PHE294, GLU323 and VAL324) and NAD. Moreover, HK improved mitochondrial function to enhance lipolysis, through decreasing the acetylated long-chain acyl-CoA dehydrogenase level. In CDHFD-fed mice, HK (2.5 and 10 mg/Kg) treatment obviously prevented lipid accumulation in the liver. And co-treatment of the AMPK inhibitor, Compound C, almost abolished the above changes. Conclusions: These results suggest that HK could ameliorate lipotoxicity in hepatocytes by activating SIRT3-AMPK-lipophagy axis, which might be a potential therapeutic agent against NAFLD.

KeywordHepatocytes Honokiol Lipid Accumulation Lipolysis Lipophagy Sirt3
DOI10.1186/s13020-021-00528-w
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaIntegrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS SubjectIntegrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000716940900001
Scopus ID2-s2.0-85118919204
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorRuan, Shuangchen; Li, Rongsong; Guo, Bing; Lin, Ligen
Affiliation1.College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Avenida da Universidade, Macao
3.College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen, 3002 Lantian Road, Pingshan District, China
4.The Department of Pathophysiology, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research On Common Chronic Diseases), College of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Liu, Jingxin,Zhang, Tian,Zhu, Jianzhong,et al. Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy[J]. Chinese Medicine,2021,16(1).
APA Liu, Jingxin,Zhang, Tian,Zhu, Jianzhong,Ruan, Shuangchen,Li, Rongsong,Guo, Bing,&Lin, Ligen.(2021).Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy.Chinese Medicine,16(1).
MLA Liu, Jingxin,et al."Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy".Chinese Medicine 16.1(2021).
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