雌马酚干预改善油酸钠诱导的HepG2细胞脂肪变性

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雌马酚干预改善油酸钠诱导的HepG2细胞脂肪变性

基础医学 | 更新时间：2026-01-09

- 雌马酚干预改善油酸钠诱导的HepG2细胞脂肪变性
- Equol intervention ameliorates steatosis in HepG2 cells induced by sodium oleate
- 陆军军医大学学报 2023年45卷第3期页码：202-208
- 作者机构：
  
  400037 重庆, 陆军军医大学(第三军医大学)第二附属医院营养科
- 作者简介：
  
  [ 王建，E-mail: wangjian_1996@aliyun.com WANG Jian, E-mail: wangjian_1996@aliyun.com
- 基金信息：
  
  国家自然基金面上项目(81973040)
- DOI：10.16016/j.2097-0927.202207014
  中图分类号： R151.41;R363.22;R575.5
- 收稿：2022-07-04，
  
  修回：2022-07-21，
  
  纸质出版：2023-02-15
- 稿件说明：
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张贵明, 倪向敏, 崔涵强, 等. 雌马酚干预改善油酸钠诱导的HepG2细胞脂肪变性[J]. 陆军军医大学学报, 2023,45(3):202-208.

Guiming ZHANG, Xiangmin NI, Hanqiang CUI, et al. Equol intervention ameliorates steatosis in HepG2 cells induced by sodium oleate[J]. Journal of Army Medical University, 2023, 45(3): 202-208.
张贵明, 倪向敏, 崔涵强, 等. 雌马酚干预改善油酸钠诱导的HepG2细胞脂肪变性[J]. 陆军军医大学学报, 2023,45(3):202-208. DOI： 10.16016/j.2097-0927.202207014.

Guiming ZHANG, Xiangmin NI, Hanqiang CUI, et al. Equol intervention ameliorates steatosis in HepG2 cells induced by sodium oleate[J]. Journal of Army Medical University, 2023, 45(3): 202-208. DOI： 10.16016/j.2097-0927.202207014.

摘要

目的

2

观察雌马酚(equol

Eq)对油酸钠(sodium oleate

NaOL)诱导的HepG2细胞脂肪变性的影响，并探讨其作用机制。

方法

2

体外培养HepG2细胞，以不同浓度(0、0.12、0.24、0.36、0.48、0.60、0.72 mmol/L)的NaOL处理48 h诱导细胞脂肪变性。油红O染色观察细胞内脂滴蓄积情况，并测定细胞TG含量，采用CCK-8法确定诱导肝细胞脂肪变性的适宜NaOL处理浓度和Eq干预的浓度范围。将细胞分为对照组，NaOL组，NaOL+Eq低、中、高浓度组(10

-7

、10

-6

、10

-5

mol/L)，NaOL+雌二醇干预组(estradiol

E2

10

-7

mol/L)。Eq干预48 h后检测细胞TG，油红O染色观察细胞内脂滴蓄积情况，qRT-PCR和Western blot检测细胞SREBP-1c、FAS、PPARα及CPT-1A mRNA和蛋白的表达。

结果

2

NaOL浓度为0.24 mmol/L时，对HepG2细胞活力无明显影响，同时细胞内TG含量明显增加，出现大量脂滴聚集；与NaOL组相比，Eq或E2干预可以降低NaOL诱导的HepG2细胞内脂滴蓄积，显著减少细胞内TG含量(

P

<

0.05)，显著降低细胞SREBP-1c和FAS的mRNA和蛋白表达水平(

P

<

0.05)，显

著升高PPARα和CPT-1A的mRNA和蛋白表达水平(

P

<

0.05)。

结论

2

Eq可有效改善NaOL诱导的HepG2细胞脂肪变性，可能与Eq降低SREBP-1c和FAS表达，同时升高PPARα和CPT-1A表达有关。

Abstract

Objective

2

To observe the effect of equol (Eq) intervention on sodium oleate (NaOL)-induced steatosis in HepG2 cells and study its mechanism of action.

Methods

2

HepG2 cells were treated with different concentrations of NaOL (0

0.12

0.24

0.36

0.48

0.60 and 0.72 mmol/L) for 48 h to induce cell steatosis. Oil red O staining was used to observe the accumulation of intracellular lipid droplets

and triglyceride (TG) content was measured. CCK-8 assay was employed to determine the optimal concentration of NaOL in the inducement of hepatic steatosis and the concentration range for Eq intervention. Then HepG2 cells were randomly divided into 6 groups: control group

NaOL group

NaOL+low-

medium- and high-dose Eq groups (10

-7

10

-6

and 10

-5

mol/L)

NaOL+estradiol intervention group (E2

10

-7

mol/L). After Eq intervention for 48 h

cellular TG content was detected

and Oil red O staining was adopted to observe the accumulation of intracellular lipid droplets

and the expression of SREBP-1c

FAS

PPARα and CPT-1A at mRNA and protein levels was detected by qRT-PCR and Western blotting

respectively.

Results

2

NaOL of 0.24 mmol/L showed no significant effect on the viability of HepG2 cells

but significantly increased intracellular TG content and accumulated a large number of lipid droplets. Compared with the NaOL group

Eq or E2 intervention reduced the intracellular lipid droplet accumulation in HepG2 cells induced by NaOL

significantly decreased the intracellular TG content (

P

<

0.05)

down-regulated the mRNA and protein expression levels of SREBP-1c and FAS (

P

<

0.05)

and up-regulated those of PPARα and CPT-1A (

P

<

0.05).

Conclusion

2

Eq could effectively improve NaOL-induced steatosis in HepG2 cells

and it may be related to its inhibiting SREBP-1c and FAS expression

while enhancing PPARα and CPT-1A expression.

关键词

Keywords

references

European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease[J]. J Hepatol, 2016, 64(6): 1388-1402. DOI:10.1016/j.jhep.2015.11.004.

YOUNOSSI Z M. Non-alcoholic fatty liver disease—A global public health perspective[J]. J Hepatol, 2019, 70(3): 531-544. DOI:10.1016/j.jhep.2018.10.033.

IPSEN D H, LYKKESFELDT J, TVEDEN-NYBORG P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease[J]. Cell Mol Life Sci, 2018, 75(18): 3313-3327. DOI:10.1007/s00018-018-2860-6.

MONTAGNER A, POLIZZI A, FOUCHÉE, et al . Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD[J ] . Gut, 2016, 65(7): 1202-1214. DOI:10.1136/gutjnl-2015-310798.

AHMED M H, BYRNE C D. Modulation of sterol regulatory element binding proteins (SREBPs) as potential treatments for non-alcoholic fatty liver disease (NAFLD)[J]. Drug Discov Today, 2007, 12(17/18): 740-747. DOI:10.1016/j.drudis.2007.07.009.

PALMISANO B T, ZHU L, STAFFORD J M. Role of estrogens in the regulation of liver lipid metabolism[J]. Adv Exp Med Biol, 2017, 1043: 227-256. DOI:10.1007/978-3-319-70178-3_12.

LEE C B, KIM J, JUNG Y. Potential therapeutic application of estrogen in gender disparity of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J]. Cells, 2019, 8(10): 1259. DOI:10.3390/cells8101259.

ZHANG S M, KUMARI S, GU Y Q, et al . Soy food intake is inversely associated with newly diagnosed nonalcoholic fatty liver disease in the TCLSIH cohort study[J ] . J Nutr, 2020, 150(12): 3280-3287. DOI:10.1093/jn/nxaa297.

WANG X M, WANG Y, XU W L, et al . Dietary isoflavones intake is inversely associated with non-alcoholic fatty liver disease, hyperlipidaemia and hypertension[J ] . Int J Food Sci Nutr, 2022, 73(1): 60-70. DOI:10.1080/09637486.2021.1910630.

PANNEERSELVAM S, PACKIRISAMY R M, BOBBY Z, et al . Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity)[J ] . J Nutr Biochem, 2016, 38: 57-69. DOI:10.1016/j.jnutbio.2016.08.007.

XIAO C W, WOOD C M, WEBER D, et al . Dietary supplementation with soy isoflavones or replacement with soy proteins prevents hepatic lipid droplet accumulation and alters expression of genes involved in lipid metabolism in rats[J ] . Genes Nutr, 2014, 9(1): 373. DOI:10.1007/s12263-013-0373-3.

MAYO B, VÁZQUEZ L, FLÓREZ A B. Equol: a bacterial metabolite from the daidzein isoflavone and its presumed beneficial health effects[J]. Nutrients, 2019, 11(9): 2231. DOI:10.3390/nu11092231.

张贵明, 倪向敏, 崔涵强, 等. 雌马酚干预对高脂饮食诱导的去卵巢大鼠非酒精性脂肪肝的影响[J]. 陆军军医大学学报, 2022, 44(21): 2129-2137. DOI: 10.16016/j.2097-0927.202204122.

ZHANG G M, NI X M, CUI H Q, et al . Effect of equol intervention on high-fat diet-induced non-alcoholic fatty liver disease in ovariectomized rats[J ] . J Army Med Univ, 2022, 44(21): 2129-2137. DOI: 10.16016/j.2097-0927.202204122.

CHEN X Y, WANG C, HUANG Y Z, et al . Nonalcoholic fatty liver disease shows significant sex dimorphism[J ] . World J Clin Cases, 2022, 10(5): 1457-1472. DOI:10.12998/wjcc.v10.i5.1457.

DONNELLY K L, SMITH C I, SCHWARZENBERG S J, et al . Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease[J ] . J Clin Invest, 2005, 115(5): 1343-1351. DOI:10.1172/JCI23621..

SILVA A K S, PEIXOTO C A. Role of peroxisome proliferator-activated receptors in non-alcoholic fatty liver disease inflammation[J]. Cell Mol Life Sci, 2018, 75(16): 2951-2961. DOI:10.1007/s00018-018-2838-4.

CAMPOREZ J P, JORNAYVAZ F R, LEE H Y, et al . Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance[J ] . Endocrinology, 2013, 154(3): 1021-1028. DOI:10.1210/en.2012-1989.

PIGHON A, GUTKOWSKA J, JANKOWSKI M, et al . Exercise training in ovariectomized rats stimulates estrogenic-like effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver[J ] . Metabolism, 2011, 60(5): 629-639. DOI:10.1016/j.metabol.2010.06.012.

PAQUETTE A, WANG D H, JANKOWSKI M, et al . Effects of ovariectomy on PPAR alpha, SREBP-1c, and SCD-1 gene expression in the rat liver[J ] . Menopause, 2008, 15(6): 1169-1175. DOI:10.1097/gme.0b013e31817b8159.

LIU H, ZHONG H, LENG L, et al . Effects of soy isoflavone on hepatic steatosis in high fat-induced rats[J ] . J Clin Biochem Nutr, 2017, 61(2): 85-90. DOI:10.3164/jcbn.16-98.

SAKAMOTO Y, KANATSU J, TOH M, et al . The dietary isoflavone daidzein reduces expression of pro-inflammatory genes through PPARα/γ and JNK pathways in adipocyte and macrophage co-cultures[J ] . PLoS One, 2016, 11(2): e0149676. DOI:10.1371/journal.pone.0149676.

KIM M H, PARK J S, JUNG J W, et al . Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism[J ] . Int J Obes (Lond), 2011, 35(8): 1019-1030. DOI:10.1038/ijo.2010.256.

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