Cholesterol, stearic and palmitic acids in the liver in nonalcoholic steatohepatitis of different severity according to the data of highly effective liquid chromatography-mass spectrometry

Authors

  • V. A. Tumanskiy Zaporizhzhia State Medical University,
  • S. V. Fen’ Zaporizhzhia State Medical University,
  • B. A. Varinskyi Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1237.2016.3.87485

Keywords:

Steatohepatitis, Cholesterol, Stearic Acid, Palmitic Acid, Chromato-mass-spectrometry

Abstract

It is known that higher saturated fatty acids (HSFA) having the lipotoxicity, play an important role in the development of non-alcoholic steatohepatitis (NASH), however, the results of research of cholesterol and HSFA in the liver with NASH of varying severity, as obtained by high performance liquid chromatography-mass spectrometry (HPLC-MS), have not been published yet.

The aim is to investigate the indicators of cholesterol, stearic and palmitic acids in the liver of the deceased patients suffering from non-alcoholic steatohepatitis with varying degrees of severity, and to compare them with indicators of blood plasma during the life of these patients.

Materials and methods. The conducted parallel posthumous pathomorphologic and HPLC-MS analysis of the liver of 25 patients, aged 53–88, who suffered during the life time of NASH and 10 deceased patients without the evidence of NASH, as well as a retrospective analysis of clinical and laboratory data in the medical records of these patients.

Results. It is found that the level of cholesterol in the liver increases from 0.42 (0.11; 4.49) mg/g to 7.10 (5.03; 8.25) mg/g (U=3.000; p=0.016) with increasing severity of NASH from S0 to S3. A statistically significant relationship between the content in the liver of stearic and palmitic acids takes place in patients with NASH (γ =0.681; p=0.001). Between the severity of NASH (y), as well as the elevated level of palmitic (x1) and stearic (x2) acids in the liver the significant relationship (y=0.83x1; R2=0.33 and y=1.13x2; R2=0.37) takes place.

Conclusions. In patients with the severe S3 mixed NASH periportal and intermediary zones of the liver lobules (LL) the significantly increased levels of stearic and palmitic acids in the liver were observed. In the severe combined total S3 NASH there is a statistically significant correlation between the severity of steatohepatitis (y), and cholesterol in the liver (x1) and cholesterol (x2) in the blood plasma (у=0.36х1+0.10х2; R2=0,91). In the severe S3 macrovesicular NASH of central and intermediate zones of LL a positive correlation between the elevated levels of total cholesterol in the blood plasma and high-density lipoproteins takes place.

References

Loomba, R. & Sanyal, A. J. (2013) The global NAFLD epidemic. Nature Reviews Gastroenterology and Hepatology, 10(11), 686–690. doi: 10.1038/nrgastro.2013.171.

Ono, H., Tanaka, A., Nakazato, K., Hasegawa, Y., Kim, K. I., Kim, S.R., et al. (2016) Stress-induced Biomarkers in Liver with Non-alcohol Fatty Liver Diseases and Non-alcohol Steatohepatitis. The Kitakanto Medical Journal, 64(1), 79–80.

Schuppan, D. & Schattenberg, J. M. (2013) Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J. Gastroenterol. Hepatol, 28(1), 68–76. doi: 10.1111/jgh.12212.

Subramanian, S., Goodspeed, L., Wang, S., Kim, J., Zeng, L., Ioannou, G. N., et al (2011) Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice. J. Lipid Res, 52(9), 1626–1635. doi: 10.1194/jlr.M016246.

Sumera, K. (2013) The contribution of vascular adhesion protein-1 to glucose

and lipid homeostasis in the liver. Institute of Biomedical Research, 370.

Loomba, R., Quehenberger, O., Armando, A. & Dennis, E. A. (2015) Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. J. Lipid Res, 56(1), 185–192. doi: 10.1194/jlr.P055640.

Rasband, W. S. (1997–2016) Image. J. Bethesda, Maryland. Retrived from: http://imagej.nih.gov/ij/.

Kleiner, D. E., Brunt, E. M., Natta, van M., & Behling, C. (2005). Design and validation of a histological scoring system for nonalcoholic fatty liver disease. J. Hepatology, 41(6), 1313–1321. doi: 10.1002/hep.20701.

Puri, P., Wiest, M. M., Cheung,O., Mirshahi, F., Sargeant, C., Min, H.K., et al. (2009) The plasma lipidomic analysis of nonalcoholic fatty liver disease. J.Hepatology, 46(4), 1081–1090.

Feldstein, A. E., Lopez, R., Tamimi, T. A., Yerian, L., Chung, Y. M., Berk, M., et al. (2010) Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J. Lipid Res, 51(10), 3046–3054. doi: 10.1194/jlr.M007096.

Caligiuri, A., Gentilini, A. & Marra, F. (2016) Molecular Pathogenesis of NASH. J. Mol. Sci, 17(9), 1–34. doi: 10.3390/ijms17091575.

Musso, G., Gambino, R. & Cassader, M. (2013) Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis. Prog Lipid Res, 52(1), 175–191. doi: 10.1016/j.plipres.2012.11.002.

Siddiqui, M. S., Cheang, K. L., Luketic, V. A., Boyett, S., Idowu, M. O., Patidar, K., et al. (2015) Nonalcoholic Steatohepatitis (NASH) Is Associated With A Decline In Pancreatic Beta Cell (β-Cell) Function. Dig Dis Sci, 60(8), 2529–2537. doi: 10.1007/s10620-015-3627-7.

Barreyro, F. J., Kobayashi, S., Bronk, S. F., Werneburg, N. W., Malhi, H. & Gores, G. J. (2007) Transcriptional Regulation of Bim by FoxO3A Mediates Hepatocyte Lipoapoptosis. J. Biol. Chem, 282(37), 141–157. doi: 10.1074/jbc.M704391200.

Takaki, A., Kawai, D. & Yamamoto, K. (2013) Multiple hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH). J. Mol. Sci, 14(10), 20704–20728. doi: 10.3390/ijms141020704.

Takeshita, Y., Takamura, T., Honda, M., Kita, Y., Zen, Y., Kato, K., et al. (2014) The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. J.Diabetologia, 57(5), 878–890. doi: 10.1007/s00125-013-3149-9.

Wree, A., McGeough, M. D., Peña, C. A., Schlattjan, M., Li, H., Inzaugarat, M. E., et al (2014) NLRP3 inflammasome activation is required for fibrosis development in NAFLD. J. Mol. Med, 92(10), 1069–1082. doi: 10.1007/s00109-014-1170-1.

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1.
Tumanskiy VA, Fen’ SV, Varinskyi BA. Cholesterol, stearic and palmitic acids in the liver in nonalcoholic steatohepatitis of different severity according to the data of highly effective liquid chromatography-mass spectrometry. Pathologia [Internet]. 2016Dec.23 [cited 2024Dec.25];(3). Available from: http://pat.zsmu.edu.ua/article/view/87485

Issue

No. 3 (2016)

Section

Original research

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