Protective effect of equol on bone in postmenopausal rats with nonalcoholic fatty liver disease

Hanqiang CUI; Xiangmin NI; Guiming ZHANG; Zhe XU; Shuo LI; Jian WANG

doi:10.16016/j.2097-0927.202210126

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Protective effect of equol on bone in postmenopausal rats with nonalcoholic fatty liver disease

Basic Medicine | 更新时间：2026-01-09

- Protective effect of equol on bone in postmenopausal rats with nonalcoholic fatty liver disease
- Journal of Army Medical University Vol. 45, Issue 5, Pages: 407-416(2023)
- 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：
- 基金信息：
  
  the General Program of National Nature Science Foundation of China(81973040);the National Natural Science Foundation for Young Scholars of China(81602855)
- DOI：10.16016/j.2097-0927.202210126
  CLC： R322.71;R575.5;R977.12
- Received：26 October 2022，
  
  Revised：2023-01-06，
  
  Published：15 March 2023
- 稿件说明：
移动端阅览
Hanqiang CUI, Xiangmin NI, Guiming ZHANG, et al. Protective effect of equol on bone in postmenopausal rats with nonalcoholic fatty liver disease[J]. Journal of Army Medical University, 2023, 45(5): 407-416.
DOI：

Hanqiang CUI, Xiangmin NI, Guiming ZHANG, et al. Protective effect of equol on bone in postmenopausal rats with nonalcoholic fatty liver disease[J]. Journal of Army Medical University, 2023, 45(5): 407-416. DOI： 10.16016/j.2097-0927.202210126.

摘要

目的

观察雌马酚(equol，Eq)对绝经后非酒精性脂肪肝病(nonalcoholic fatty liver disease，NAFLD)大鼠的骨保护效应，并探讨其作用机制。

方法

选取6周龄雌性Sprague Dawley(SD)大鼠48只，随机分为对照组、模型组、低剂量Eq组[20 mg/(kg·d)]、中剂量Eq组[40 mg/(kg·d)]、高剂量Eq组[80 mg/(kg·d)]和雌二醇干预组[estradiol，E2，0.25 mg/(kg·d)]，每组8只，对照组给予假手术及正常饮食，其余各组给予卵巢切除术(OVX)合并高脂饮食(HFD)。16周后测量大鼠体质量、体长，计算BMI和Lee’s指数，检测各组大鼠的骨密度和骨微结构变化；麻醉后处死大鼠并取材，检测大鼠血清雌激素、TNF-α和IL-6水平，肝脏和股骨组织学检查观察形态学变化；采用Western blot和qRT-PCR检测肝和骨组织中胰岛素样生长因子-1 (insulin-like growth factor-1

IGF-1)表达水平。

结果

模型组大鼠BMI和Lee’s指数显著升高(

0.05)，肝组织损伤明显，雌激素和骨密度水平较对照组显著下降(

0.05)，骨显微结构破坏严重，提示绝经后NAFLD合并明显骨损伤；Eq和E2干预能显著升高大鼠血清雌激素和骨密度水平(

0.0

5)，改善骨显微结构，降低BMI、Lee’s指数和血清TNF-α、IL-6水平(

0.05)，减轻肝和骨组织脂质累积，升高肝和骨组织IGF-1蛋白和mRNA表达水平(

0.05)。

结论

Eq能改善绝经后NAFLD大鼠的骨损伤，具有骨保护作用，其部分机制可能与Eq促进IGF-1表达和减轻炎症反应有关。

Abstract

Objective

To observe the osteoprotective effect of equol (Eq) on postmenopausal rats with nonalcoholic fatty liver disease (NAFLD)

and to explore its underlying mechanism.

Methods

Forty-eight 6-week-old female Sprague-Dawley (SD) rats were randomly divided into control group

model group

low-

middle- and high-dose Eq groups [20

40 and 80 mg/(kg·d)]

and estradiol intervention group [E2

0.25 mg/(kg·d)]

with 8 rats in each group. The control group was given sham operation and normal diet. The other groups were given ovariectomy (OVX) combined with high-fat diet. After 16 weeks

the body weight and length of rats were measured

BMI and Lee's index were calculated

and the changes of bone mineral density (BMD) and bone microstructure of rats were detected. After anesthesia

the rats were killed to detect the levels of serum estrogen

TNF-α and IL-6. The liver and femur tissues were observed for morphological changes

and the expression of insulin-like growth factor-1 (IGF-1) in the liver and bone was detected by Western blotting and qRT-PCR.

Results

In the model group

BMI and Lee's index were increased significantly

the liver tissue was obviously injured

the estrogen level and BMD were obvioiusly decreased

and the bone microstructure was seriously damaged

suggesting that postmenopausal NAFLD was complicated with obvious bone injury. The treatment of Eq or E2 increased the level of serum estrogen and BMD

decreased BMI

Lee's index and serum TNF-α and IL-6 levels

attenuated steatosis and lipid accumulation in bone microstructure

and enhanced the expression of IGF-1 at protein and mRNA level in the liver and bone.

Conclusion

Eq can improve the bone injury of postmenopausal NAFLD rats and shows a bone protective effect. The mechanism may partially be related to Eq promoting the expression of IGF-1 and reducing inflammation.

关键词

Keywords

references

ARCEO-MENDOZA R M, CAMACHO P M. Postmenopausal osteoporosis: latest guidelines[J]. Endocrinol Metab Clin North Am, 2021, 50(2): 167-178. DOI: 10.1016/j.ecl.2021.03.009.

SHEN Z, CEN L, CHEN X F, et al . Increased risk of low bone mineral density in patients with non-alcoholic fatty liver disease: a cohort study[J ] . Eur J Endocrinol, 2020, 182(2): 157-164. DOI: 10.1530/EJE-19-0699.

鲍晓雪, 王娜, 李玉坤. 肥胖与骨质疏松症关系的研究进展[J]. 中华临床医师杂志(电子版), 2015, 9(14): 2749-2753. DOI: 10.3877/cma.j.issn. 1674-0785. 2015. 14. 030.

BAO X X, WANG N, LI Y K. Advances in the relationship between obesity and osteoporosis[J]. Chin J Clin Electron Ed, 2015, 9(14): 2749-2753. DOI: 10.3877/cma.j.issn.1674-0785.2015.14.030.

LEE D Y, PARK J K, HUR K Y, et al . Association between nonalcoholic fatty liver disease and bone mineral density in postmenopausal women[J ] . Climacteric, 2018, 21(5): 498-501. DOI: 10.1080/13697137.2018.1481380.

MANSON J E, CHLEBOWSKI R T, STEFANICK M L, et al . Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative Randomized Trials[J ] . JAMA, 2013, 310(13): 1353-1368. DOI: 10.1001/jama.2013.278040.

田玉慧, 李万里, 杨献军, 等. 大豆异黄酮对成骨细胞生长因子表达的影响[J]. 中国公共卫生, 2003, 19(12): 1438-1439. DOI: 10.11847/zgggws2003-19-12-17.

TIAN Y H, LI W L, YANG X J, et al . Effect of soybean isoflavone on ICF-1 expression of osteoblstic cells[J ] . China Public Health, 2003, 19(12): 1438-1439. DOI: 10.11847/zgggws2003-19-12-17.

MUTHYALA R S, JU Y H, SHENG S B, et al . Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta[J ] . Bioorg Med Chem, 2004, 12(6): 1559-1567. DOI: 10.1016/j.bmc.2003.11.035.

陈小香, 邓伟民, 魏秋实, 等. 从GH/IGF-1轴与PI3K/Akt通路探讨老年骨质疏松症的发病机制[J]. 中国骨质疏松杂志, 2015, 21(11): 1412-1415. DOI: 10.3969/j.issn.1006-7108.2015.11.026.

CHEN X X, DENG W M, WEI Q S, et al . Investigation of the pathogenesis of senile osteoporosis from GH/IGF-1 axis and PI3K/Akt pathway[J ] . Chin J Osteoporos, 2015, 21(11): 1412-1415. DOI: 10. 3969/j.issn.1006-7108.2015.11.026.

李崇, 罗晓婷, 纪舒妤, 等. 炎症因子在骨质疏松发病机理中的研究进展[J]. 中国骨质疏松杂志, 2021, 27(10): 1516-1522. DOI: 10.3969/j.issn.1006-7108.2021.10.022.

LI C, LUO X T, JI S Y, et al . Research on the progress of inflammatory factors in the pathogenesis of osteoporosis[J ] . Chin J Osteoporos, 2021, 27(10): 1516-1522. DOI: 10.3969/j.issn.1006-7108.2021.10.022.

陈景娴, 栾晓军, 陈劲松. 非酒精性脂肪肝与骨密度关联研究的相关进展[J]. 中国骨质疏松杂志, 2018, 24(10): 1396-1400. DOI: 10.3969/j.issn.1006-7108.2018.10.025.

CHEN J X, LUAN X J, CHEN J S. Progress in research on the association between nonalcoholic fatty liver disease and bone mineral density[J]. Chin J Osteoporos, 2018, 24(10): 1396-1400. DOI: 10.3969/j.issn.1006-7108.2018.10.025.

CARDIM H J P, LOPES C M C, GIANNELLA-NETO D, et al . The insulin-like growth factor-I system and hormone replacement therapy[J ] . Fertil Steril, 2001, 75(2): 282-287. DOI: 10.1016/S0015-0282(00)01691-5.

GEORGE K S, MUÃ±OZ J, AKHAVAN N S, et al . Is soy protein effective in reducing cholesterol and improving bone health?[J ] . Food Funct, 2020, 11(1): 544-551. DOI: 10.1039/C9FO01081E.

LIN I C, YAMASHITA S, MURATA M, et al . Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice[J ] . J Nutr Biochem, 2016, 32: 101-106. DOI: 10.1016/j.jnutbio.2016.02.012.

MALAIRUNGSAKUL O, WIWATANADATE P. Factors related to osteoporosis of postmenopausal women in Phayao, Thailand[J]. Arch Osteoporos, 2013, 8(1): 154. DOI: 10.1007/s11657-013-0154-z.

CHEN H J, YANG H Y, HSUEH K C, et al . Increased risk of osteoporosis in patients with nonalcoholic fatty liver disease: a population-based retrospective cohort study[J ] . Medicine, 2018, 97(42): e12835. DOI: 10.1097/MD.0000000000012835.

CHEN D Z, XU Q M, WU X X, et al . The combined effect of nonalcoholic fatty liver disease and metabolic syndrome on osteoporosis in postmenopausal females in Eastern China[J ] . Int J Endocrinol, 2018, 2018: 2314769. DOI: 10.1155/2018/2314769.

GUNARATNAM K, VIDAL C, GIMBLE J M, et al . Mechanisms of palmitate-induced lipotoxicity in human osteoblasts[J ] . Endocrinology, 2014, 155(1): 108-116. DOI: 10.1210/en.2013-1712.

SETCHELL K D R, CLERICI C, LEPHART E D, et al . S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora[J ] . Am J Clin Nutr, 2005, 81(5): 1072-1079. DOI: 10.1093/ajcn/81.5.1072.

朱磊, 路瑛丽, 冯连世, 等. 不同配方高脂饲料构建SD大鼠肥胖模型的实验研究[J]. 中国运动医学杂志, 2016, 35(7): 642-647. DOI: 10.16038/j.1000-6710.2016.07.006.

ZHU L, LU Y L, FENG L S, et al . Experimental study on establishing obese model of male SD rat with different fat percentages in high-fat diet[J ] . Chin J Sports Med, 2016, 35(7): 642-647. DOI: 10.16038/j.1000-6710.2016.07.006.

FRIEDMAN S L, NEUSCHWANDER-TETRI B A, RINELLA M, et al . Mechanisms of NAFLD development and therapeutic strategies[J ] . Nat Med, 2018, 24(7): 908-922. DOI: 10.1038/s41591-018-0104-9.

MONTEIRO R, AZEVEDO I. Chronic inflammation in obesity and the metabolic syndrome[J]. Mediators Inflamm, 2010, 2010: 289645. DOI: 10.1155/2010/289645.

MUNDY G R. Osteoporosis and inflammation[J]. Nutr Rev, 2007, 65(12 pt 2): S147-S151. DOI: 10.1111/j.1753-4887.2007.tb00353.x.

陈怡洁, 金雪静, 王雪, 等. 雌激素及炎症因子与绝经后骨质疏松症相关研究进展[J]. 国际妇产科学杂志, 2020, 47(6): 712-715.

CHEN Y J, JIN X J, WANG X, et al . Research progress on the relationship between estrogen, inflammatory factors and postmenopausal osteoporosis[J ] . J Int Obstet Gynecol, 2020, 47(6): 712-715.

SUBEDI L, JI E, SHIN D, et al . Equol, a dietary daidzein gut metabolite attenuates microglial activation and potentiates neuroprotection in vitro[J ] . Nutrients, 2017, 9(3): 207. DOI: 10.3390/nu9030207.

GAO S T, LV Z T, ZHOU C K, et al . Association between IGF-1 polymorphisms and risk of osteoporosis in Chinese population: a meta-analysis[J ] . BMC Musculoskelet Disord, 2018, 19(1): 141. DOI: 10.1186/s12891-018-2066-y.

覃玉君. 脂肪肝与骨质疏松症的相关性[J]. 医学理论与实践, 2020, 33(2): 207-208, 206. DOI: 10.19381/j.issn.1001-7585.2020.02.012.

QIN Y J. Correlation between fatty liver and osteoporosis[J]. J Med Theory Pract, 2020, 33(2): 207-208, 206. DOI: 10.19381/j.issn.1001-7585.2020.02.012.

薛歆, 董进. 雌激素对成骨细胞增殖及TGF-β1、IGF-1 mRNA表达的影响[J]. 中国医药指南, 2013, 11(14): 88-90. DOI: 10.15912/j.cnki.gocm.2013.14.365.

XUE X, DONG J. Effects of estrogen on osteoblast proliferation and TGF-β1 and IGF-1 mRNA expression[J]. Guide China Med, 2013, 11(14): 88-90. DOI: 10.15912/j.cnki.gocm.2013.14.365.

Y ZHAO H, M LIU J, NING G, et al . Relationships between insulin-like growth factor-I (IGF-I) and OPG, RANKL, bone mineral density in healthy Chinese women[J ] . Osteoporos Int, 2008, 19(2): 221-226. DOI: 10.1007/s00198-007-0440-y.

高美. 成年雌性大鼠骨重建机理及大豆甙元干预作用研究[D]. 南京: 南京师范大学, 2009.

GAO M. Studyon the mechanism of bone remodeling in adult rats and the intervention effect of daidzein[D]. Nanjing: Nanjing Normal University, 2009. 10. 7666/d. d183248.

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Department of Orthopaedics, Center of Orthopaedic Surgery, First Affiliated Hospital of Army Medical University (Third Military Medical University)

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