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Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease (NAFLD). It remains unknown whether dietary intake of condensed tannins (CTs) have distinguishable effects to alleviate liver damage caused by a high cholesterol diet. Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks, and given CTs treatment at a dosage of 200 mg/(kg·day) at the same time. The results indicated that compared with mice fed a normal diet, a high cholesterol diet group resulted in significant weight loss, dysregulation of lipid metabolism in blood and liver, and oxidative stress in the liver, but CTs treatment dramatically reversed these negative effects. Hematoxylin and eosin (H&E) staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake. CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation. Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.


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Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Show Author's information Xiangxin Lia,1Yijing Pua,b,1Bangdi LiucXiaoming FangaWenjun PengaWeibo Jiangb( )Wenli Tiana,( )
Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
Academy of Agricultural Planning and Engineering, Ministry of Agriculture and Rural Affairs, Beijing 100125, China

1 The authors contribute equally to this article.

Peer review under responsibility of Tsinghua University Press.

Abstract

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease (NAFLD). It remains unknown whether dietary intake of condensed tannins (CTs) have distinguishable effects to alleviate liver damage caused by a high cholesterol diet. Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks, and given CTs treatment at a dosage of 200 mg/(kg·day) at the same time. The results indicated that compared with mice fed a normal diet, a high cholesterol diet group resulted in significant weight loss, dysregulation of lipid metabolism in blood and liver, and oxidative stress in the liver, but CTs treatment dramatically reversed these negative effects. Hematoxylin and eosin (H&E) staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake. CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation. Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Keywords: Transcriptomic analysis, Liver injury, Antioxidants, Condensed tannins, High cholesterol

References(45)

[1]

T. Tsuchida, Y.A. Lee, N. Fujiwara, et al., A simple diet- and chemicalinduced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer, J. Hepatol. 69 (2018) 385-395. https://doi.org/10.1016/j.jhep.2018.03.011.

[2]

E. Buzzetti, M. Pinzani, E.A. Tsochatzis, The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD), Metabolism 65 (2016) 1038-1048. https://doi.org/10.1016/j.metabol.2015.12.012.

[3]

C.D. Byrne, G. Targher, NAFLD: a multisystem disease, J. Hepatol. 62 (2015) S47-S64. https://doi.org/10.1016/j.jhep.2014.12.012.

[4]

G.N. Ioannou, The role of cholesterol in the pathogenesis of NASH, Trends Endocrinol. Metab. 27 (2016) 84-95. https://doi.org/10.1016/j.tem.2015.11.008.

[5]

M.C. Morrison, W. Liang, P. Mulder, et al., Mirtoselect, an anthocyaninrich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE*3 Leiden mice, J. Hepatol. 62 (2015) 1180-1186. https://doi.org/10.1016/j.jhep.2014.12.011.

[6]

P. du Souich, G. Roederer, R. Dufour, Myotoxicity of statins: mechanism of action, Pharmacol. Ther. 175 (2017) 1-16. https://doi.org/10.1016/j.pharmthera.2017.02.029.

[7]

P.M. Hunter, R.A. Hegele, Functional foods and dietary supplements for the management of dyslipidaemia. Nat. Rev. Endocrinol. 13 (2017) 278-288. https://doi.org/10.1038/nrendo.2016.210.

[8]

Y. Tan, J. Kim, J. Cheng, Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats, World J. Gastroenterol. 23 (2017) 3805. https://doi.org/10.3748/wjg.v23.i21.3805.

[9]

C.H. Peng, J.J. Cheng, M.H. Yu, Solanum nigrum polyphenols reduce body weight and body fat by affecting adipocyte and lipid metabolism, Food Funct. 11 (2020) 483-492. https://doi.org/10.1039/C9FO02240F.

[10]

J.A. Domínguez-Avila, G.A. González-Aguilar, E. Alvarez-Parrilla, Modulation of PPAR expression and activity in response to polyphenolic compounds in high fat diets, Int. J. Mol. Sci. 17 (2016) 1002. https://doi.org/10.3390/ijms17071002.

[11]

C.M. John, S. Arockiasamy, Inhibition of palmitic acid induced adipogenesis by natural polyphenols in 3T3-L1 adipocytes, In vitro Cell. Dev. Biol. Anim. (2022) 1-12. https://doi.org/10.1039/C6FO00401F.

[12]

D.Y. Xie, R.A. Dixon, Proanthocyanidin biosynthesis–still more questions than answers? Phytochemistry 66 (2005) 2127-2144. https://doi.org/10.1016/j.phytochem.2005.01.008.

[13]

A. Rauf, M. Imran, T. Abu-Izneid, et al., Proanthocyanidins: a comprehensive review, Biomed. Pharmacother. 116 (2019) 108999. https://doi.org/10.1016/j.biopha.2019.108999.

[14]

X. Zeng, Z. Du, X. Ding, et al., Characterization of the direct interaction between apple condensed tannins and cholesterol in vitro, Food Chem. 309 (2020) 125762. https://doi.org/10.1016/j.foodchem.2019.125762.

[15]

X. Li, W. Jiao, W. Zhang, et al., Characterizing the interactions of dietary condensed tannins with bile salts, J. Agric. Food Chem. 67 (2019) 9543-9550. https://doi.org/10.1021/acs.jafc.9b03985.

[16]

X. Li, H. Jiang, Y. Pu, et al., Inhibitory effect of condensed tannins from banana pulp on cholesterol esterase and mechanisms of interaction, J. Agric. Food Chem. 67 (2019) 14066-14073. https://doi.org/10.1021/acs.jafc.9b05212.

[17]

N. Matsuzawa, T. Takamura, S. Kurita, et al., Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet, Hepatology 46 (2007) 1392-1403. https://doi.org/10.1002/hep.21874.

[18]

X. Han, W. Li, D. Huang, et al., Polyphenols from hawthorn peels and fleshes differently mitigate dyslipidemia, inflammation and oxidative stress in association with modulation of liver injury in high fructose diet-fed mice, Chem. Biol. Interact. 257 (2016) 132-140. https://doi.org/10.1016/j.cbi.2016.08.002.

[19]

C. Cocco, G.V. Melis, G.L. Ferri, Embedding media for cryomicrotomy: an applicative reappraisal, Appl. Immunohistochem. Mol. Morphol. 11 (2003) 274-280. https://doi.org/10.1097/00129039-200309000-00012.

[20]

A. Dobin, C.A. Davis, F. Schlesinger, et al., STAR: ultrafast universal RNA-seq aligner, Bioinformatics 29 (2012) 15-21. https://doi.org/10.1093/bioinformatics/bts635.

[21]

S. Anders, P.T. Pyl, W. Huber, HTSeq–a Python framework to work with high-throughput sequencing data, Bioinformatics 31 (2015) 166-169. https://doi.org/10.1093/bioinformatics/btu638.

[22]

M.I. Love, W. Huber, S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol. 15 (2014) 550. https://doi.org/10.1186/s13059-014-0550-8.

[23]

F. Yuan, X. Pan, L. Chen, et al., Analysis of protein–protein functional associations by using gene ontology and KEGG pathway, BioMed Res. Int. 2019 (2019). https://doi.org/10.1155/2019/4963289

[24]

Z. Duan, Y. Zhang, C. Zhu, et al., Structural characterization of phosphorylated Pleurotus ostreatus polysaccharide and its hepatoprotective effect on carbon tetrachloride-induced liver injury in mice, J. Biol. Macromol. 162 (2020) 533-547. https://doi.org/10.1016/j.ijbiomac.2020.06.107

[25]

Q.Q. Zhang, L.G. Lu, Nonalcoholic fatty liver disease: dyslipidemia, risk for cardiovascular complications, and treatment strategy, JCTH 3 (2015) 78. https://doi.org/10.14218/JCTH.2014.00037.

[26]

K.K. Patel, K. Kashfi, Lipoproteins and cancer: The role of HDL-C, LDL-C, and cholesterol-lowering drugs, Biochem. Pharmacol. (2021) 114654. https://doi.org/10.1016/j.bcp.2021.114654.

[27]

B. Zhu, Z. Wang, L. Lei, et al., Transcriptome reveals overview of Ca2+ dose-dependent metabolism disorders in zebrafish larvae after Cd2+ exposure, J. Environ. Sci. (China) 125 (2023) 480-491. https://doi.org/10.1016/j.jes.2021.12.009.

[28]

J. Luo, H. Yang, B.L. Song, Mechanisms and regulation of cholesterol homeostasis, Nat. Rev. Mol. Cell Biol. 21 (2020) 225-245. https://doi.org/10.1038/s41580-019-0190-7.

[29]

F. Marra, G. Svegliati-Baroni, Lipotoxicity and the gut-liver axis in NASH pathogenesis, J. Hepatol. 68 (2018) 280-295. https://doi.org/10.1016/j.jhep.2017.11.014.

[30]

G. Svegliati-Baroni, I. Pierantonelli, P. Torquato, et al., Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease, Free Radic. Biol. Med. 144 (2019) 293-309. https://doi.org/10.1016/j.freeradbiomed.2019.05.029.

[31]

G.N. Ioannou, The role of cholesterol in the pathogenesis of NASH, Trends Endocrinol. Metab. 27(2) (2016) 84-95. https://doi.org/10.1016/j.tem.2015.11.008.

[32]

C.F. Aquino, L.C.C. Salomão, S. Ribeiro, et al., Carbohydrates, phenolic compounds and antioxidant activity in pulp and peel of 15 banana cultivars, Rev. Bras. Frutic. 38 (2016). https://doi.org/10.1590/0100-29452016090.

[33]

L.P.G. Rebello, A.M. Ramos, P.B. Pertuzatti, et al., Flour of banana (Musa AAA) peel as a source of antioxidant phenolic compounds, Food Res. Int. 55 (2014) 397-403. https://doi.org/10.1016/j.foodres.2013.11.039.

[34]

Z. Ge, W. Zhu, J. Peng, et al., Persimmon tannin regulates the expression of genes critical for cholesterol absorption and cholesterol efflux by LXRα independent pathway, J. Funct. Foods 23 (2016) 283-293. https://doi.org/10.1016/j.jff.2016.02.033.

[35]

S. Seki, T. Kitada, T. Yamada, et al., In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases, J. Hepatol. 37 (2002) 56-62. https://doi.org/10.1016/S0168-8278(02)00073-9.

[36]

A.R. Mridha, A. Wree, A.A. Robertson, et al., NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice, J. Hepatol. 66 (2017) 1037-1046. https://doi.org/10.1016/j.jhep.2017.01.022.

[37]

W. Li, D. Huang, A. Gao, et al., Stachyose increases absorption and hepatoprotective effect of tea polyphenols in high fructose-fed mice, Mol. Nutr. Food Res. 60 (2016) 502-510. https://doi.org/10.1002/mnfr.201500547.

[38]

R. Li, Z. Jia, M.A. Trush, Defining ROS in biology and medicine, React. Oxyg. Species (Apex.) 1 (2016) 9. https://doi.org/10.20455/ros.2016.803.

[39]

S. Gaweł, M. Wardas, E. Niedworok, et al., Malondialdehyde (MDA) as a lipid peroxidation marker, Wiadomosci lekarskie (Warsaw, Poland: 1960). 57 (2004) 453-455.

[40]

R. Zhu, Y. Wang, L. Zhang, et al., Oxidative stress and liver disease, Hepatol. Res. 42 (2012) 741-749. https://doi.org/10.1111/j.1872-034X.2012.00996.x.

[41]

B.F. Asztalos, E.J. Schaefer, K.V. Horvath, et al., Role of LCAT in HDL remodeling: investigation of LCAT deficiency states, J. Lipid Res. 48(3) (2007) 592-599. https://doi.org/10.1194/jlr.M600403-JLR200.

[42]

G.W. Go, A. Mani, Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis, Yale. J. Biol. Med. 85 (2012) 19. https://doi.org/10.17816/maj25755-22554.

[43]

L. Yu, J. Li-Hawkins, R.E. Hammer, et al., Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol, J. Clin. Investig. 110 (2002) 671-680. https://doi.org/10.1172/JCI16001.

[44]

J.Y. Chiang, Recent advances in understanding bile acid homeostasis, F1000Research 6 (2017). https://doi.org/10.12688/f1000research.12449.1.

[45]

D. Garcia, R.J. Shaw, AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance, Mol. Cell 66 (2017) 789-800. https://doi.org/10.1016/j.molcel.2017.05.032.

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Received: 16 July 2022
Revised: 14 August 2022
Accepted: 11 September 2022
Published: 25 September 2023
Issue date: March 2024

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© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2013CB127106).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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