Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes.
Background: Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. He...
| Publicado en: | Nutrition & Metabolism Vol. 18; no. 1; pp. 1 - 14 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
BioMed Central
1/19/2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=148189162&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 148189162 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17437075 1CYX jtl: Nutrition & Metabolism issn: 17437075 maglogo: N pubinfo: dt: 1/19/2021 vid: 18 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 148189162 148189162 148189162 10.1186/s12986-021-00540-9 148189162 ppf: 1 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes. aug: au: Xu, Tiantian Song, Qing Zhou, Li Yang, Wenwen Wu, Xiangyao Qian, Qianyu Chai, Hui Han, Qiang Pan, Hongzhi Dou, Xiaobing Li, Songtao affil: College of Basic Medicine and Public Health, Zhejiang Chinese Medical University, 310053, Hangzhou, China sug: subj: Acids, Carbocyclic Pharmacodynamics Phytochemicals Pharmacodynamics Metabolic Diseases Prevention and Control Cell Death Drug Effects Autophagy Drug Effects Signal Transduction Drug Effects AMP-Activated Protein Kinases Drug Effects Transferases Drug Effects Hepatocytes Drug Effects Animal Studies Mice Plant Extracts Pharmacodynamics Free Radical Scavengers Drug Effects Acids, Carbocyclic Administration and Dosage Cell Viability Drug Effects Lactate Dehydrogenase Analysis Caspases Metabolism Reactive Oxygen Species Drug Effects Mitochondria Drug Effects Membrane Potentials Drug Effects Blotting, Western Methods Polymerase Chain Reaction Methods Interleukins Drug Effects ab: Background: Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective effect of ferulic acid against palmitate-induced lipotoxicity and clarified its potential mechanisms in AML-12 hepatocytes. Methods: AML-12 mouse hepatocytes were exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate treatment. Cell viability was detected by measuring lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase-3. Intracellular reactive oxygen species content and mitochondrial membrane potential were analysed by fluorescent probes. The potential mechanisms were explored by molecular biological methods, including Western blotting and quantitative real-time PCR, and were further verified by siRNA interference. Results: Our data showed that ferulic acid significantly inhibited palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxygen species accumulation, and decreased inflammatory factor activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, whereas autophagy suppression blocked the protective effect of ferulic acid against lipotoxicity. Ferulic acid-activated autophagy, which was triggered by SIRT1 upregulation, was mechanistically involved in its anti-lipotoxicity effects. SIRT1 silencing blocked most beneficial changes induced by ferulic acid. Conclusions: We demonstrated that the phytochemical ferulic acid, which is found in plant-based food, protected against hepatic lipotoxicity, through the SIRT1/autophagy pathway. Increased intake of ferulic acid-enriched food is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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