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Licensed Unlicensed Requires Authentication Published by De Gruyter March 15, 2022

Establishment and metabonomics analysis of nonalcoholic fatty liver disease model in golden hamster

  • Cui-Zhu Zhao , Lin Jiang , Wen-Yan Li , Guang Wu , Jie Chen , Li-Hua Dong , Min Li , Wei Jiang , Ji-Xiao Zhu , Yan-Ping Gao , Qin-Ge Ma ORCID logo EMAIL logo , Guo-Yue Zhong EMAIL logo and Rong-Rui Wei ORCID logo EMAIL logo

Abstract

The aim is to establish a model of nonalcoholic fatty liver disease (NAFLD) caused by feeding with high-fat, high-fructose, and high-cholesterol diet (HFFCD) in golden hamsters, and to investigate the characteristics of the NAFLD model and metabolite changes of liver tissue. Golden hamsters were fed HFFCD or control diets for six weeks. Body weight, abdominal fat index, and liver index was assessed, serum parameters, hepatic histology, and liver metabolites were examined. The results showed that body weight, abdominal fat, and liver index of hamsters were significantly increased in the model group, the level of serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) were significantly increased in model group as well, and high density lipoprotein-cholesterol (HDL-C) was significantly decreased. In addition, lipid deposition in liver tissue formed fat vacuoles of different sizes. Metabonomics analysis of the liver showed that the metabolic pathways of sphingolipid, glycerophospholipids, and arginine biosynthesis were disordered in the NAFLD model. The modeling method is simple, short time, and uniform. It can simulate the early fatty liver caused by common dietary factors, and provides an ideal model for the study of the initial pathogenesis and therapeutic drugs for NAFLD.


Corresponding authors: Qin-Ge Ma, Key Laboratory of Modern Preparation of Traditional Medicine of Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China, E-mail: ; and Guo-Yue Zhong and Rong-Rui Wei, Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China, E-mail: (G.-Y. Zhong), (R.R. Wei)

Funding source: Science and Technology Project of Jiangxi Health Commission

Award Identifier / Grant number: 202211413

Funding source: Scientific Research Project of Jiangxi Administration of Traditional Chinese Medicine

Award Identifier / Grant number: 2019A018

Funding source: Jiangxi University of Chinese Medicine Graduate Innovation Fund

Award Identifier / Grant number: JZYC21S75

Funding source: State Scholarship Fund of China Scholarship Council

Award Identifier / Grant number: 202008360033

Funding source: Jiangxi Provincial Natural Science Foundation

Award Identifier / Grant number: 20202BAB216036

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported by Science and Technology Project of Jiangxi Health Commission (202211413), Scientific Research Project of Jiangxi Administration of Traditional Chinese Medicine (2019A018), Jiangxi University of Chinese Medicine Graduate Innovation Fund (JZYC21S75), State Scholarship Fund of China Scholarship Council (202008360033), and Jiangxi Provincial Natural Science Foundation (20202BAB216036).

  3. Conflict of interest statement: The authors have declared that there is no conflict of interest.

References

1. Toplak, H, Stauber, R, Sourij, H. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease: guidelines, clinical reality and health economic aspects. Diabetologia 2016;59:1148–9. https://doi.org/10.1007/s00125-016-3941-4.Search in Google Scholar

2. Byrne, CD, Targher, G. NAFLD: a multisystem disease. J Hepatol 2015;62:47–64. https://doi.org/10.1016/j.jhep.2014.12.012.Search in Google Scholar

3. Lonardo, A, Byrne, CD, Caldwell, SH, Cortez-Pinto, H, Targher, G. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73–84. https://doi.org/10.1002/hep.28584.Search in Google Scholar

4. Wu, YK, Zheng, Q, Zou, BY, Yeo, YH, Li, XH, Li, J, et al.. The epidemiology of NAFLD in Mainland China with analysis by adjusted gross regional domestic product: a meta-analysis. Hepatol Int 2020;14:259–69. https://doi.org/10.1007/s12072-020-10023-3.Search in Google Scholar

5. Chon, YE, Kim, KJ, Jung, KS, Kim, SU, Park, JY, Kim, DY, et al.. The relationship between type 2 diabetes mellitus and non-alcoholic fatty liver disease measured by controlled attenuation parameter. Yonsei Med J 2016;57:885–92. https://doi.org/10.3349/ymj.2016.57.4.885.Search in Google Scholar

6. Alessandro, M, Stefano, B, Lonardo, A, Giovanni, T. Cardiovascular disease and myocardial abnormalities in nonalcoholic fatty liver disease. Dig Dis Sci 2016;61:1246–67. https://doi.org/10.1007/s10620-016-4040-6.Search in Google Scholar

7. Petta, S, Argano, C, Colomba, D, Camma, C, Marco, VD, Cabibi, D, et al.. Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease. J Hepatol 2015;62:928–33. https://doi.org/10.1016/j.jhep.2014.11.030.Search in Google Scholar

8. Younossi, ZM, Blissett, D, Blissett, R, Henry, L, Stepanova, M, Younossi, Y, et al.. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology 2016;64:1577–86. https://doi.org/10.1002/hep.28785.Search in Google Scholar

9. Hadi, E, Maryam, N, Forough, F, Marjan, R, Hassan, EZ, Azita, H. An accessible and pragmatic experimental model of nonalcoholic fatty liver disease. Middle East J Digest Dis 2016;8:109–15. https://doi.org/10.15171/mejdd.2016.15.Search in Google Scholar

10. Majid, B, Adel, M, Jamshid, K, Nasrin, S, Ghasem, S, Farjam, G, et al.. Hepatoprotective effect of parthenolide in rat model of nonalcoholic fatty liver disease. Immunopharmacol Immunotoxicol 2017;39:233–42. https://doi.org/10.1080/08923973.2017.1327965.Search in Google Scholar

11. Wu, YL, Zhou, F, Jiang, HT, Wang, ZJ, Hua, C, Zhang, YS. Chicory (Cichorium intybus L.) polysaccharides attenuate high-fat diet induced non-alcoholic fatty liver disease via AMPK activation. Int J Biol Macromol 2018;118:886–95. https://doi.org/10.1016/j.ijbiomac.2018.06.140.Search in Google Scholar

12. Jiang, MZ, Wu, N, Chen, X, Wang, WJ, Chu, Y, Liu, H, et al.. Pathogenesis of and major animal models used for nonalcoholic fatty liver disease. J Int Med Res 2019;47:1453–66. https://doi.org/10.1177/0300060519833527.Search in Google Scholar

13. Dominika, M, Agnieszka, L, Karolina, D, Karolina, SZ, Izabela, G, Marta, SM, et al.. Diet-induced rat model of gradual development of non-alcoholic fatty liver disease (NAFLD) with lipopolysaccharides (LPS) secretion. Diagnostics 2019;9:205. https://doi.org/10.3390/diagnostics9040205.Search in Google Scholar

14. Wong, SK, Chin, KY, Ahmad, F, Ima-Nirwana, S. Regulation of inflammatory response and oxidative stress by tocotrienol in a rat model of non-alcoholic fatty liver disease. J Funct Foods 2020;74:104209. https://doi.org/10.1016/j.jff.2020.104209.Search in Google Scholar

15. Cui, P, Shi, JM, Ma, T, Rao, L, Tong, XY, Hu, W, et al.. Long-term androgen-induced nonalcoholic fatty liver disease in a polycystic ovary syndrome mouse model is related to mitochondrial dysfunction. Reprod Dev Med 2021;5:71–80. https://doi.org/10.4103/2096-2924.320884.Search in Google Scholar

16. Chen, YP, Xiao, BQ, Zhang, JH, Liu, WW, Li, CQ. New method of non-alcoholic fatty liver disease mouse models and mechanism about immune cells. Chin Pharmacol Bull 2018;34:882–6. https://doi.org/10.3969/j.issn.1001-1978.2018.06.028.Search in Google Scholar

17. Dai, L, Lu, YH, Zhang, M, Tian, F, Incretion, DO. Effects of ethanol extract of Moringa oleifera leaves on oxidative stress and lipid in nonalcoholic fatty liver disease mice model. Guihaia 2019;39:855–62. https://doi.org/10.11931/guihaia.gxzw201805016.Search in Google Scholar

18. Goedeke, L, Bates, J, Vatner, DF, Perry, RJ, Wang, T, Ramirez, R, et al.. Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents. Hepatology 2018;68:2197–211. https://doi.org/10.1002/hep.30097.Search in Google Scholar

19. Tsutsumi, K, Hagi, A, Inoue, Y. The relationship between plasma high density lipoprotein cholesterol levels and cholesteryl ester transfer protein activity in 6 species of healthy experimental animals. Biol Pharm Bull 2002;24:579–81. https://doi.org/10.1248/bpb.24.579.Search in Google Scholar

20. Bravo, E, Cantafora, A, Calcabrini, A, Oryu, G. Why prefer the golden Syrian hamster (Mesocricetus auratus) to the Wistar rat in experimental studies on plasma lipoprotein metabolism. Comp Biochem Physiol Part B Compara Biochem 1994;107:347–55.10.1016/0305-0491(94)90058-2Search in Google Scholar

21. Bhathena, J, Kulamarva, A, Martoni, C, Urbanska, A, Malhotra, M, Paul, A, et al.. Diet-induced metabolic hamster model of nonalcoholic fatty liver disease. Diabetes Metab Syndrome Obes Targets Ther 2011;4:195–203. https://doi.org/10.2147/DMSO.S18435.Search in Google Scholar

22. Friedman, SL, Neuschwander-Tetri, BA, Mary, R, Sanyal, AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018;24:908–22. https://doi.org/10.1038/s41591-018-0104-9.Search in Google Scholar

23. Zelber, S, Ivancovskyn, WD, Isakov, NF, Webb, MO. High red and processed meat consumption is associated with non-alcoholic fatty liver disease and insulin resistance. J Hepatol 2018;68:1239–46. https://doi.org/10.1016/j.jhep.2018.01.015.Search in Google Scholar

24. Samuel, VT. Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab Tem 2011;22:60–5. https://doi.org/10.1016/j.tem.2010.10.003.Search in Google Scholar

25. Oftic, S, Cohen, DE, Kahn, CR. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci 2016;61:1282–93. https://doi.org/10.1007/s10620-016-4054-0.Search in Google Scholar

26. Kim, YC, Seok, S, Byun, S, Bo, K, Yang, Z, Guo, G, et al.. AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle. Nat Commun 2018;9:540. https://doi.org/10.1038/s41467-018-03060-y.Search in Google Scholar

27. Fu, SN, Ling, Y, Ping, L, Oliver, H, Lee, D, Winston, H, et al.. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 2011;473:528–31. https://doi.org/10.1038/nature09968.Search in Google Scholar

28. Chave, J, Summers, S. A ceramide-centric view of insulin resistance. Cell Metabol 2012;15:585–94. https://doi.org/10.1016/j.cmet.2012.04.002.Search in Google Scholar

29. Guri, Y, Colombi, M, Dazert, E, Hindupur, SK, Roszik, J, Moes, S, et al.. mTORC2 promotes tumorigenesis via lipid synthesis. Cancer Cell 2017;32:807–23. https://doi.org/10.1016/j.ccell.2017.11.011.Search in Google Scholar

30. Luukkonen, PK, Zhou, Y, Sädevirta, S, Leivonen, M, Arola, J, Orešič, M, et al.. Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease. J Hepatol 2016;64:1167–75. https://doi.org/10.1016/j.jhep.2016.01.002.Search in Google Scholar

Received: 2021-07-16
Accepted: 2022-02-19
Published Online: 2022-03-15
Published in Print: 2022-05-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 24.9.2023 from https://www.degruyter.com/document/doi/10.1515/znc-2021-0201/pdf
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