Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Metabonomics Application on Screening Serum Biomarkers of Golden Hamsters with Nonalcoholic Steatohepatitis Induced by High-Fat Diet

Author(s): Jingjing Hu, Yueliang Shen and Yunwen Chen*

Volume 26, Issue 13, 2023

Published on: 31 March, 2023

Page: [2280 - 2292] Pages: 13

DOI: 10.2174/1386207326666230223095745

Price: $65

Abstract

Background: Nonalcoholic steatohepatitis (NASH) is a common liver injury which will develop into advanced fibrosis and cirrhosis. This study was designed to identify the different serum metabolites of NASH hamsters and predict the diagnosis biomarkers for NASH.

Methods: Golden hamsters were randomly divided into a control group that received a normal diet and a NASH group that received a high-fat diet (HFD). After 12 weeks of feeding, the body and liver weight of the hamsters were monitored. Serum biochemical parameters and liver histopathological changes were analyzed. Moreover, an untargeted metabolomics analysis based on a GCTOF/ MS system was performed to identify the serum differential metabolites between the NASH and control groups.

Results: The liver weight was increased in the NASH group, accompanied by significantly higher levels of serum TC, TG, ALT, AST, LDL-C, and lower HDL-C. HE, Masson, and oil red O staining showed the hepatocyte structure destroyed, lipid droplets accumulated, and fibers proliferated in the NASH group. Furthermore, 63 differential metabolites were identified by metabolomic analysis. Lipids and fatty acids were significantly up-regulated in the NASH group. The top 9 differential metabolites included cholesterol, methyl phosphate, taurine, alpha-tocopherol, aspartic acid, etc. Metabolites were mainly involved in amino acid metabolism (glycine, cysteine, taurine), spermine, fatty acid biosynthesis, urea cycle, bile acid metabolism pathways, etc.

Conclusion: Metabonomics analysis identified 63 differential metabolites in the serum of NASH hamsters; among them, lipids and fatty acids had a key role and may be used as biomarkers for the early diagnosis of NASH.

« Previous Next »
Graphical Abstract

[1]
Tu, L.N.; Showalter, M.R.; Cajka, T.; Fan, S.; Pillai, V.V.; Fiehn, O.; Selvaraj, V. Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice. Sci. Rep., 2017, 7(1), 6120.
[http://dx.doi.org/10.1038/s41598-017-05040-6] [PMID: 28733574]
[2]
Han, J.; Dzierlenga, A.L.; Lu, Z.; Billheimer, D.D.; Torabzadeh, E.; Lake, A.D.; Li, H.; Novak, P.; Shipkova, P.; Aranibar, N.; Robertson, D.; Reily, M.D.; Lehman-McKeeman, L.D.; Cherrington, N.J. Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model. Obesity, 2017, 25(6), 1069-1076.
[http://dx.doi.org/10.1002/oby.21855] [PMID: 28452429]
[3]
Ajmera, V.; Loomba, R. Imaging biomarkers of NAFLD, NASH, and fibrosis. Mol. Metab., 2021, 50, 101167.
[http://dx.doi.org/10.1016/j.molmet.2021.101167] [PMID: 33460786]
[4]
Younossi, Z.; Henry, L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology, 2016, 150(8), 1778-1785.
[http://dx.doi.org/10.1053/j.gastro.2016.03.005] [PMID: 26980624]
[5]
Cardoso, A.C.; de Figueiredo-Mendes, C.; A Villela-Nogueira, C. Current management of NAFLD/NASH. Liver Int., 2021, 41(Suppl. 1), 89-94.
[http://dx.doi.org/10.1111/liv.14869] [PMID: 34155799]
[6]
Wong, R.J.; Aguilar, M.; Cheung, R.; Perumpail, R.B.; Harrison, S.A.; Younossi, Z.M.; Ahmed, A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology, 2015, 148(3), 547-555.
[http://dx.doi.org/10.1053/j.gastro.2014.11.039] [PMID: 25461851]
[7]
Caligiuri, A.; Gentilini, A.; Marra, F. Molecular pathogenesis of NASH. Int. J. Mol. Sci., 2016, 17(9), 1575.
[http://dx.doi.org/10.3390/ijms17091575] [PMID: 27657051]
[8]
Chalasani, N.; Younossi, Z.; Lavine, J.E.; Charlton, M.; Cusi, K.; Rinella, M.; Harrison, S.A.; Brunt, E.M.; Sanyal, A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the study of liver diseases. Hepatology, 2018, 67(1), 328-357.
[http://dx.doi.org/10.1002/hep.29367] [PMID: 28714183]
[9]
Younossi, Z.; Anstee, Q.M.; Marietti, M.; Hardy, T.; Henry, L.; Eslam, M.; George, J.; Bugianesi, E. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(1), 11-20.
[http://dx.doi.org/10.1038/nrgastro.2017.109] [PMID: 28930295]
[10]
Khalifa, A.; Rockey, D.C. The utility of liver biopsy in 2020. Curr. Opin. Gastroenterol., 2020, 36(3), 184-191.
[http://dx.doi.org/10.1097/MOG.0000000000000621] [PMID: 32097176]
[11]
Rowe, I.A. Decision making for liver biopsy in NASH, not so FAST? Lancet Gastroenterol. Hepatol., 2020, 5(4), 332-334.
[http://dx.doi.org/10.1016/S2468-1253(19)30406-6] [PMID: 32027859]
[12]
Mato, J.M.; Lu, S.C. Where are we in the search for noninvasive nonalcoholic steatohepatitis biomarkers? Hepatology, 2011, 54(4), 1115-1117.
[http://dx.doi.org/10.1002/hep.24642] [PMID: 21898494]
[13]
Laíns, I.; Gantner, M.; Murinello, S.; Lasky-Su, J.A.; Miller, J.W.; Friedlander, M.; Husain, D. Metabolomics in the study of retinal health and disease. Prog. Retin. Eye Res., 2019, 69, 57-79.
[http://dx.doi.org/10.1016/j.preteyeres.2018.11.002] [PMID: 30423446]
[14]
Bowers, J.; Hughes, E.; Skill, N.; Maluccio, M.; Raftery, D. Detection of hepatocellular carcinoma in hepatitis C patients: Biomarker discovery by LC–MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 966, 154-162.
[http://dx.doi.org/10.1016/j.jchromb.2014.02.043] [PMID: 24666728]
[15]
Shi, C.; Wang, L.; Zhou, K.; Shao, M.; Lu, Y.; Wu, T. Targeted metabolomics identifies differential serum and liver amino acids biomarkers in rats with alcoholic liver disease. J. Nutr. Sci. Vitaminol., 2020, 66(6), 536-544.
[http://dx.doi.org/10.3177/jnsv.66.536] [PMID: 33390395]
[16]
Elbadawy, M.; Yamanaka, M.; Goto, Y.; Hayashi, K.; Tsunedomi, R.; Hazama, S.; Nagano, H.; Yoshida, T.; Shibutani, M.; Ichikawa, R.; Nakahara, J.; Omatsu, T.; Mizutani, T.; Katayama, Y.; Shinohara, Y.; Abugomaa, A.; Kaneda, M.; Yamawaki, H.; Usui, T.; Sasaki, K. Efficacy of primary liver organoid culture from different stages of non-alcoholic steatohepatitis (NASH) mouse model. Biomaterials, 2020, 237, 119823.
[http://dx.doi.org/10.1016/j.biomaterials.2020.119823] [PMID: 32044522]
[17]
Dei Cas, M.; Casagni, E.; Arnoldi, S.; Gambaro, V.; Roda, G. Screening of new psychoactive substances (NPS) by gaschromatography/time of flight mass spectrometry (GC/MS-TOF) and application to 63 cases of judicial seizure. Forensic Sci Int Synerg, 2019, 1, 71-78.
[http://dx.doi.org/10.1016/j.fsisyn.2019.04.003] [PMID: 32411957]
[18]
Imajo, K.; Yoneda, M.; Kessoku, T.; Ogawa, Y.; Maeda, S.; Sumida, Y.; Hyogo, H.; Eguchi, Y.; Wada, K.; Nakajima, A. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Int. J. Mol. Sci., 2013, 14(11), 21833-21857.
[http://dx.doi.org/10.3390/ijms141121833] [PMID: 24192824]
[19]
Ioannou, G.N.; Nagana Gowda, G.A.; Djukovic, D.; Raftery, D. Distinguishing NASH histological severity using a multiplatform metabolomics approach. Metabolites, 2020, 10(4), 168.
[http://dx.doi.org/10.3390/metabo10040168] [PMID: 32344559]
[20]
Carreres, L.; Jílková, Z.M.; Vial, G.; Marche, P.N.; Decaens, T.; Lerat, H. Modeling diet-induced nafld and nash in rats: A comprehensive review. Biomedicines, 2021, 9(4), 378.
[http://dx.doi.org/10.3390/biomedicines9040378] [PMID: 33918467]
[21]
Yang, Q.H.; Xu, Y.J.; Feng, G.F.; Hu, C.F.; Zhang, Y.P.; Cheng, S.B.; Wang, Y.P.; Gong, X.W. p38 Mapk signal pathway involved in anti-inflammatory effect of chaihu-shugan-san and shen-lingbai-zhu-san on hepatocyte in non-alcoholic steatohepatitis rats. Afr. J. Tradit. Complement. Altern. Med., 2013, 11(1), 213-221.
[http://dx.doi.org/10.4314/ajtcam.v11i1.34] [PMID: 24653580]
[22]
Nakatsuka, A.; Matsuyama, M.; Yamaguchi, S.; Katayama, A.; Eguchi, J.; Murakami, K.; Teshigawara, S.; Ogawa, D.; Wada, N.; Yasunaka, T.; Ikeda, F.; Takaki, A.; Watanabe, E.; Wada, J. Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. Sci. Rep., 2016, 6(1), 21721.
[http://dx.doi.org/10.1038/srep21721] [PMID: 26883167]
[23]
Kalhan, S.C.; Guo, L.; Edmison, J.; Dasarathy, S.; McCullough, A.J.; Hanson, R.W.; Milburn, M. Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism, 2011, 60(3), 404-413.
[http://dx.doi.org/10.1016/j.metabol.2010.03.006] [PMID: 20423748]
[24]
Gauthier, M.S.; Favier, R.; Lavoie, J.M. Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats. Br. J. Nutr., 2006, 95(2), 273-281.
[http://dx.doi.org/10.1079/BJN20051635] [PMID: 16469142]
[25]
Seike, T.; Boontem, P.; Yanagi, M.; Li, S.; Kido, H.; Yamamiya, D.; Nakagawa, H.; Okada, H.; Yamashita, T.; Harada, K.; Kikuchi, M.; Shiraishi, Y.; Ozaki, N.; Kaneko, S.; Yamashima, T.; Mizukoshi, E. Hydroxynonenal causes hepatocyte death by disrupting lysosomal integrity in nonalcoholic steatohepatitis. Cell. Mol. Gastroenterol. Hepatol., 2022, 14(4), 925-944.
[http://dx.doi.org/10.1016/j.jcmgh.2022.06.008] [PMID: 35787976]
[26]
Kwak, D.H.; Kim, J.S.; Chang, K.T.; Choo, Y.K. Aristolochia manshuriensis Kom ethyl acetate extract protects against high-fat diet-induced non-alcoholic steatohepatitis by regulating kinase phosphorylation in mouse. J. Vet. Sci., 2016, 17(3), 279-287.
[http://dx.doi.org/10.4142/jvs.2016.17.3.279] [PMID: 26726030]
[27]
Boland, M.L.; Oró, D.; Tølbøl, K.S.; Thrane, S.T.; Nielsen, J.C.; Cohen, T.S.; Tabor, D.E.; Fernandes, F.; Tovchigrechko, A.; Veidal, S.S.; Warrener, P.; Sellman, B.R.; Jelsing, J.; Feigh, M.; Vrang, N.; Trevaskis, J.L.; Hansen, H.H. Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source. World J. Gastroenterol., 2019, 25(33), 4904-4920.
[http://dx.doi.org/10.3748/wjg.v25.i33.4904] [PMID: 31543682]
[28]
Marchesini, G.; Petta, S.; Dalle Grave, R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology, 2016, 63(6), 2032-2043.
[http://dx.doi.org/10.1002/hep.28392] [PMID: 26663351]
[29]
Pierantonelli, I.; Svegliati-Baroni, G. Nonalcoholic fatty liver disease: Basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 2019, 103(1), e1-e13.
[http://dx.doi.org/10.1097/TP.0000000000002480] [PMID: 30300287]
[30]
Van Rooyen, D.; Larter, C.; Haigh, W.; Yeh, M.; Ioannou, G.; Kuver, R.; Lee, S.; Teoh, N.; Farrell, G. Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology, 2011, 141(4), 1393-1403.
[http://dx.doi.org/10.1053/j.gastro.2011.06.040]
[31]
Jia, W.; Wei, M.; Rajani, C.; Zheng, X. Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell, 2021, 12(5), 411-425.
[http://dx.doi.org/10.1007/s13238-020-00804-9] [PMID: 33252713]
[32]
Chiang, J.Y.L. Targeting bile acids and lipotoxicity for NASH treatment. Hepatol. Commun., 2017, 1(10), 1002-1004.
[http://dx.doi.org/10.1002/hep4.1127] [PMID: 29404437]
[33]
Gentile, C.L.; Nivala, A.M.; Gonzales, J.C.; Pfaffenbach, K.T.; Wang, D.; Wei, Y.; Jiang, H.; Orlicky, D.J.; Petersen, D.R.; Pagliassotti, M.J.; Maclean, K.N. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2011, 301(6), R1710-R1722.
[http://dx.doi.org/10.1152/ajpregu.00677.2010] [PMID: 21957160]
[34]
Jang, E.S.; Hwang, S.H.; Kim, J.W.; Jeong, S.H. Effectiveness of 4-week oral taurine treatment for muscle cramps in patients with liver cirrhosis: A single-arm pilot study. Yonsei Med. J., 2021, 62(1), 21-28.
[http://dx.doi.org/10.3349/ymj.2021.62.1.21] [PMID: 33381931]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy