Oleic acid ameliorates palmitic acid induced hepatocellular lipotoxicity by inhibition of ER stress and pyroptosis.
Background: Pyroptosis is a novel programmed cell death. It is identified as caspase-1 dependent and characterized by plasma-membrane rupture and release of proinflammatory intracellular contents inculuding IL-1 beta and IL-18. Pyroptosis is distinct from other forms of cell death, especially apopto...
| Published in: | Nutrition & Metabolism Vol. 17; no. 1; pp. 1 - 15 |
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| Main Authors: | , , , , , , , , , |
| Format: | letter pictorial research tables/charts Journal Article |
| Published: |
BioMed Central
1/30/2020
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141474704&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141474704 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17437075 1CYX jtl: Nutrition & Metabolism issn: 17437075 maglogo: N pubinfo: dt: 1/30/2020 vid: 17 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 141474704 141474704 141474704 10.1186/s12986-020-0434-8 141474704 ppf: 1 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Oleic acid ameliorates palmitic acid induced hepatocellular lipotoxicity by inhibition of ER stress and pyroptosis. aug: au: Zeng, Xing Zhu, Min Liu, Xiaohong Chen, Xuanmin Yuan, Yujia Li, Lan Liu, Jingping Lu, Yanrong Cheng, Jingqiu Chen, Younan affil: Key Laboratory of Transplant Engineering and Immunology, NHFPC sug: subj: Fatty Acids, Monounsaturated Pharmacodynamics Apoptosis Drug Effects Endoplasmic Reticulum Drug Effects Stress, Physiological Drug Effects Hepatocytes Drug Effects Lipids Metabolism Hepatotoxicity Prevention and Control Fatty Acids, Saturated Adverse Effects Nonalcoholic Fatty Liver Disease Pathology Nonalcoholic Fatty Liver Disease Prevention and Control Animal Studies Rats Cell Line Drug Effects Nucleosides Administration and Dosage Staining and Labeling Methods Interleukin 1 Drug Effects Tumor Necrosis Factor Drug Effects Enzyme-Linked Immunosorbent Assay Dietary Fats Adverse Effects Olive Oil Pharmacodynamics Blood Chemical Analysis Cell Viability Gene Expression Drug Effects RNA, Messenger Drug Effects Caspases Drug Effects Cell Membrane Drug Effects Biological Markers Drug Effects In Vitro Studies In Vivo Studies Polymerase Chain Reaction Methods Blotting, Western Fluorescent Antibody Technique Liver Anatomy and Histology Liver Metabolism ab: Background: Pyroptosis is a novel programmed cell death. It is identified as caspase-1 dependent and characterized by plasma-membrane rupture and release of proinflammatory intracellular contents inculuding IL-1 beta and IL-18. Pyroptosis is distinct from other forms of cell death, especially apoptosis that is characterized by nuclear and cytoplasmic condensation and is elicited via activation of a caspase cascade. In pyroptosis, gasdermin D (GSDMD) acts as a major executor, while NLRP3 related inflammasome is closely linked to caspase-1 activation. Given that pyroptosis has played a critical role in the progression of non-alcoholic steatohepatitis (NASH), here, we investigated whether the regulation of pyroptosis activation is responsible for the protective role of monounsaturated oleic acids in the context of hepatocellular lipotoxicity. Methods: Human hepatoma cell line HepG2 cells were exposed to palmitic acid (PA) with or without oleic acids (OA) or/and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA) for 24 h. Besides, the cells were treated with the chemical ER stressor tunicamycin (TM) with or without OA for 24 h as well. The expressions of pyroptosis and ER stress related genes or proteins were determined by real-time PCR, Western blot or immunofluorescence. The morphology of pyroptosis was detected by acridine orange and ethidium bromide (AO/EB) staining. The release of IL-1 beta and tumor necrosis factor alpha (TNF-α) was determined by ELISA. Sprague–Dawley (SD) rats were fed with high fat diet (HFD) for 16 w, then, HFD was half replaced by olive oil to observe the protective effects of olive oil. The blood chemistry were analyzed, and the liver histology and the expressions of related genes and proteins were determined in the liver tissues. Results: We demonstrated that PA impaired the cell viability and disturbed the lipid metabolism of HepG2 cells (P < 0.01), but OA robustly rescued cells from cell death (P < 0.001). More importantly, we found that instead of cell apoptosis, PA induced significant pyroptosis, evidenced by remarkably increased mRNA and protein expressions of inflammasome marker NLRP3, Caspase-1 and IL-1beta, as well as cell membrane perforation driving protein GSDMD (P < 0.05). Furthermore, we demonstrated that the PA stimulated ER stress was causally related to pyroptosis. The enhanced expressions of ER stress markers CHOP and BIP were found subcellular co-located to pyroptosis markers NLRP3 and ASC. Additionally,TM was able to induce pyroptosis like PA did, and ER stress inhibitor TUDCA was able to inhibit both PA and TM induced ER stress as well as pyroptosis. Furthermore, we demonstrated that OA substantially alleviated either PA or TM induced ER stress and pyroptosis in HepG2 cells (P < 0.01). In vivo, only olive oil supplementation did not cause significant toxicity, while HFD for 32 w obviously induced liver steatosis and inflammation in SD rats (P < 0.05). Half replacement of HFD with olive oil (a mixed diet) has remarkably ameliorated liver abnormalities, and particularly inhibited the protein expressions of either ER stress and pyroptosis markers (P < 0.05). Conclusion: Palmitic acid induced predominant pyroptosis in HepG2 cells, and ER stress may be responsible for the induction of pyroptosis and subsequent cell death. Monounsaturated oleic acids were able to ameliorate hepatocellular lipotoxicity both in vitro and in vivo, and OA mediated inhibition of ER stress and pyroptosis may be the underlying mechanisms. pubtype: Academic Journal doctype: letter pictorial research tables/charts Journal Article ougenre: Unknown language: English refInfo: holdings: @attributes: islocal: N |
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