PLANT STEROL ESTER OF &#x003b1;-LINOLENIC ACID AMELIORATES ETHANOL-INDUCED STEATOSIS AND OXIDATIVE STRESS IN HEPG2 CELLS VIA REGULATING SIRT3 EXPRESSION

HAN Yan-yang; GUO Hui-min; ZHENG Ming-ming; DONG Ya-jing; JI Shu-qi; HAN Hao

Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (1) : 52-59.

PLANT STEROL ESTER OF α-LINOLENIC ACID AMELIORATES ETHANOL-INDUCED STEATOSIS AND OXIDATIVE STRESS IN HEPG2 CELLS VIA REGULATING SIRT3 EXPRESSION

HAN Yan-yang¹, GUO Hui-min¹, ZHENG Ming-ming², DONG Ya-jing¹, JI Shu-qi¹, HAN Hao¹

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Abstract

Objective To investigate the ameliorative effect of plant sterol ester of α-linolenic acid (PS-ALA) on steatosis and oxidative stress in HepG2 cells exposed to ethanol (EtOH), and the underlying mechanism associated with the regulation of SIRT3 expression. Methods HepG2 cells were treated with EtOH and intervened by PS-ALA. The lipid accumulation in the cells was evaluated by Oil Red O staining. The level of reactive oxygen species (ROS) was detected by DCFH-DA fluorescent probe. The expression of SIRT3 was assessed by immunofluorescence staining. The protein expressions of SIRT3, PPARα, CPT-1A, SOD2 and CYP2E1 were measured by Western blot. Results Compared with the control group, the cells in the EtOH group showed a significant increase in intracellular lipid accumulation and ROS production. PS-ALA intervention significantly decreased lipid accumulation and suppressed ROS production. The results of further molecular mechanism studies showed that PS-ALA treatment significantly increased the protein expressions of SIRT3, PPARα, and CPT-1A. Meanwhile, PS-ALA treatment significantly increased the protein expression of SOD2 and decreased the protein expression of CYP2E1. Conclusion PS-ALA can inhibit EtOH-induced steatosis and oxidative stress in HepG2 cells, and its molecular mechanism is related to promoting β-oxidation of fatty acid and inhibiting oxidative stress by up-regulating SIRT3 expression.

Key words

plant sterol ester of α-linolenic acid / steatosis / SIRT3 / HepG2 cell

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HAN Yan-yang, GUO Hui-min, ZHENG Ming-ming, DONG Ya-jing, JI Shu-qi, HAN Hao. PLANT STEROL ESTER OF α-LINOLENIC ACID AMELIORATES ETHANOL-INDUCED STEATOSIS AND OXIDATIVE STRESS IN HEPG2 CELLS VIA REGULATING SIRT3 EXPRESSION[J]. Acta Nutrimenta Sinica. 2025, 47(1): 52-59

References

[1] Singal AK, Bataller R, Ahn J, et al. ACG Clinical Guideline: Alcoholic Liver Disease[J]. Am J Gastroenterol, 2018, 113:175–194.
[2] Xu H, Xiao P, Zhang F, et al. Epidemic characteristics of alcohol-related liver disease in Asia from 2000 to 2020: A systematic review and meta-analysis[J]. Liver Int, 2022, 42:1991–1998.
[3] Sarin SK, Kumar M, Eslam M, et al. Liver diseases in the Asia-Pacific region: a lancet gastroenterology & hepatology commission[J]. Lancet Gastroenterol Hepatol, 2020, 5:167–228.
[4] Hyun J, Han J, Lee C, et al. Pathophysiological aspects of alcohol metabolism in the liver[J]. Int J Mol Sci, 2021, 22:5717.
[5] Yan C, Hu W, Tu J, et al. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease[J]. J Transl Med, 2023, 21:300.
[6] Malnick SDH, Alin P, Somin M, et al. Fatty liver disease-alcoholic and non-alcoholic: similar but different[J]. Int J Mol Sci,2022, 23:16226.
[7] Ceni E, Mello T, Galli A.Pathogenesis of alcoholic liver disease: role of oxidative metabolism[J]. World J Gastroenterol, 2014, 20:17756–17772.
[8] Zhang J, Xiang H, Liu J, et al. Mitochondrial sirtuin 3: new emerging biological function and therapeutic target[J]. Theranostics, 2020, 10:8315–8342.
[9] Xu X, Zhu XP, Bai JY, et al. Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet in mice by activating SIRT3[J]. FASEB J, 2019 33:7289–7300.
[10] Zeng X, Yang J, Hu O, et al. Dihydromyricetin ameliorates nonalcoholic fatty liver disease by improving mitochondrial respiratory capacity and redox homeostasis through modulation of SIRT3 signaling[J]. Antioxid Redox Signal, 2019, 30:163–183.
[11] Jones PJH, Shamloo M, MacKay D, et al. Progress and perspectives in plant sterol and plant stanol research[J]. Nutr Rev, 2018, 76:725–746.
[12] 邓乾春, 黄凤洪, 黄庆德,等. α-亚麻酸甾醇酯的理化特性及氧化稳定性研究[J]. 天然产物研究与开发, 2012,24:370–373, 388.
[13] Han H, Li X, Guo Y, et al. Plant sterol ester of α-linolenic acid ameliorates high-fat diet-induced nonalcoholic fatty liver disease in mice: association with regulating mitochondrial dysfunction and oxidative stress via activating AMPK signaling[J]. Food Funct, 2021, 12:2171–2188.
[14] Han H, Li J, Tian L, et al. Through regulation of the SIRT1 pathway plant sterol ester of α-linolenic acid inhibits pyroptosis thereby attenuating the development of NASH in mice[J]. J Nutr Biochem, 2023, 119:109408.
[15] Osna NA, Rasineni K, Ganesan M, et al. Pathogenesis of alcohol-associated liver disease[J]. J Clin Exp Hepatol, 2022, 12:1492–1513.
[16] Kai J, Yang X, Wang, Z, et al. Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease[J]. Free Radic Biol Med, 2020, 153:89–102.
[17] Zhao X, Wang C, Dai S, et al. Quercetin protects ethanol-induced hepatocyte pyroptosis via scavenging mitochondrial ROS and promoting PGC-1α-regulated mitochondrial homeostasis in L02 cells[J]. Oxid Med Cell Longev, 2022,2022:4591134.
[18] Liu J, Chen H, Lin H, et al. Iron-frataxin involved in the protective effect of quercetin against alcohol-induced liver mitochondrial dysfunction[J]. J Nutr Biochem, 2023, 114:109258.
[19] Nagappan A, Jung DY, Kim JH, et al. Gomisin N alleviates ethanol-induced liver injury through ameliorating lipid metabolism and oxidative stress[J]. Int J Mol Sci, 2018, 19:2601.
[20] Subramaiyam N.Insights of mitochondrial involvement in alcoholic fatty liver disease[J]. J Cell Physiol, 2023, 238:2175–2190.
[21] Donde H, Ghare S, Joshi-Barve S, et al. Tributyrin inhibits ethanol-induced epigenetic repression of CPT-1A and attenuates hepatic steatosis and injury[J]. Cell Mol Gastroenterol Hepatol, 2020,9:569–585.
[22] You Y, Liu C, Liu T, et al. FNDC3B protects steatosis and ferroptosis via the AMPK pathway in alcoholic fatty liver disease[J]. Free Radic Biol Med, 2022,193:808–819.
[23] Abo-Zaid OA, Moawed FS, Ismail ES, et al. β-sitosterol attenuates high- fat diet-induced hepatic steatosis in rats by modulating lipid metabolism, inflammation and ER stress pathway[J]. BMC Pharmacol Toxicol, 2023, 24:31.
[24] Weng SW, Wu JC, Shen FC, et al. Chaperonin counteracts diet-induced non-alcoholic fatty liver disease by aiding sirtuin 3 in the control of fatty acid oxidation[J]. Diabetologia, 2023, 66:913–930.
[25] Leung TM, Lu Y.Alcoholic liver disease: from CYP2E1 to CYP2A5[J]. Curr Mol Pharmacol, 2017, 10:172–178.
[26] Gao Y, Jiang X, Yang D, et al. Roxadustat, a hypoxia-inducible factor 1α activator, attenuates both long- and short-term alcohol-induced alcoholic liver disease[J]. Front Pharmacol, 2022, 13:895710.
[27] Shi Y, Liu Y, Wang S, et al. Endoplasmic reticulum-targeted inhibition of CYP2E1 with vitamin E nanoemulsions alleviates hepatocyte oxidative stress and reverses alcoholic liver disease[J]. Biomaterials, 2022, 288:121720.
[28] Li DP, Chen YL, Jiang HY, et al. Phosphocreatine attenuates Gynura segetum-induced hepatocyte apoptosis via a SIRT3-SOD2-mitochondrial reactive oxygen species pathway[J]. Drug Des Devel Ther, 2019, 13:2081–2096.
[29] Jiao L, Hu CX, Zhang Y, et al. SIRT3 regulates levels of deacetylated SOD2 to prevent oxidative stress and mitochondrial dysfunction during oocyte maturation in pigs[J]. Microsc Microanal 2023, 29:2149–2160.
[30] Chen XQ, Peng B, Jiang HM, et al. Salvianolic acid B alleviates oxidative stress in non-alcoholic fatty liver disease by mediating the SIRT3/FOXO1 signaling pathway[J]. Chin J Nat Med, 2022, 31:698–710.