Non-alcoholic fatty liver disease (NAFLD) is the major cause of steatohepatitis, cirrhosis and hepatocellular carcinoma. High saturated fat rich diet is one of the known causes of NAFLD. Non-Alcoholic liver disease NAFLD is characterized by steatosis and upregulation of different proinflammatory cytokines, like caspase-1 dependant IL1β, type I IL1 receptor (IL1R1), and IL1 receptor antagonist (IL1Ra). Till date there is no proper treatment option available for NASH except management of obesity and food intake. Anti inflammatory drugs are used as a treatment option in atherosclerosis, where inflammatory response plays an important role. Keeping a similarity in mind the recombinant IL1Ra and inflammatory cytokine IL1β was tested as treatmet option for high fat condition in Palmitate treated HepG2 cells. The lipid metabolism pathways were tested with a purchased recombinant product as well as with THP1 and its macrophage extracted product. The major outcome was removal of storage fat from the cells by increasing the beta oxidation level. So the conclusion was that IL1Ra can play a major role in controlling the accumulated fatty level in liver cells.
| Published in | Cancer Research Journal (Volume 5, Issue 4) |
| DOI | 10.11648/j.crj.20170504.11 |
| Page(s) | 24-34 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2018. Published by Science Publishing Group |
NAFLD, IL1β, IL1Ra, THP1-Monocyte and Macrophage
| [1] | Younossi, Z. M., Stepanova, M., Afendy, M., Fang, Y., Younossi, Y., Mir, H. and Srishord, M (2011). Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 9, 524–530. |
| [2] | Cohen, J. C., Horton, J. D. and Hobbs, H. H (2011). Human fatty liver disease: old questions and new insights. Science 332, 1519–1523. |
| [3] | Sozio, M. S., Liangpunsakul, S. and Crabb, D (2010). The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis 30, 378–390. |
| [4] | Nobili, V., Cutrera, R., Liccardo, D., Pavone, M., Devito, R., Giorgio, V., Verrillo, E., Baviera, G. and Musso, G (2014). Obstructive sleep apnea syndrome affects liver histology and inflammatory cell activation in pediatric nonalcoholic fatty liver disease, regardless of obesity/insulin resistance. Am J Respir Crit Care Med 189, 66–76. |
| [5] | World Gastroenterology Organisation Global Guidelines. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis 2012. |
| [6] | Mathews, S. and Gao, B. (2013). Therapeutic Potential of Interleukin 1 Inhibitors in the Treatment of Alcoholic Liver Disease. Hepatology 57 (5), 2078–2080. |
| [7] | Kugelmas, M., Hill, D. B., Vivian, B., Marsano, L. and McClain, C. J: Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology (2003) (38), 413–419. |
| [8] | Abiru, S., Migita, K., Maeda, Y., Daikoku M., Ito, M., Ohata, K., Nagaoka, S., Matsumoto, T., Takii, Y., Kusumoto, K., et al (2006). Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis. Liver Int 26, 39–45. |
| [9] | Jarrar, M. H., Baranova, A., Collantes, R., Ranard, B., Stepanova, M., Bennett, C., Fang, Y., Elariny, H., Goodman, Z., Chandhoke, V., et al (2008). Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 27, 412–421. |
| [10] | Copaci, I., Micu, L. and Voiculescu, M (2006). The role of cytokines in non-alcoholic steatohepatitis. A review. J Gastrointestin Liver Dis 15, 363–373. |
| [11] | Zechner, R., Kienesberger, P. C., Haemmerle, G., Zimmermann, R., Lass, A (2009). Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res 50, 3–21. |
| [12] | Grønning-Wang, L. M., Bindesbøll, C. and Nebb H. I (2007). The Role of Liver X Receptor in Hepatic de novo Lipogenesis and Cross-Talk with Insulin and Glucose Signaling. IN: Baez RV, editor. Lipid Metabolism. Mol Biosyst 3, 608–619. |
| [13] | Kirovski, G., Dorn, C., Huber, H., Moleda, L, Niessen, C., Wobser, H., Schacherer, D., Buechler, C., Wiest, R. and Hellerbrand, C (2011). Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation. Exp Mol Pathol 91, 780–783. |
| [14] | Ratziu, V., Massard, J., Charlotte, F., Messous, D., Imbert-Bismut, F., Bonyhay, L., Tahiri, M., Munteanu, M., Thabut, D,, Cadranel, J. F., et al (2006). Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 6, 6. |
| [15] | Nelson, A., Torres, D. M., Morgan, A. E., Fincke, C. and Harrison, S. A (2009). A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial. J Clin Gastroenterol 43, 990–994. |
| [16] | Antonopoulos, S., Mikros, S., Mylonopoulou, M., Kokkoris, S. and Giannoulis, G (2006) Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis 184, 233–234. |
| [17] | Ekstedt, M., Franzén, L. E., Mathiesen, U. L., Holmqvist, M., Bodemar, G., and Kechagias, S (2007). Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study. J Hepatol 47, 135–141. |
| [18] | Gómez-Domínguez, E., Gisbert. J. P., Moreno-Monteagudo, J. A., García-Buey, L., and Moreno-Otero, R (2006). A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 23, 1643–1647. |
| [19] | Foster, T., Budoff, M. J., Saab, S., Ahmadi, N., Gordon, C. and, Guerci, A. D ( 2011). Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol 106, 71–77. |
| [20] | Eslami, L., Merat, S., Malekzadeh, R., Nasseri-Moghaddam, S. and Aramin, H (2013). Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database Syst Rev 12, CD008623. |
| [21] | Musso, G., Gambino, R., Cassader, M. and Pagano, G (2011). Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 43, 617–649. |
| [22] | Bugianesi, E., Pagotto, U., Manini, R., Vanni, E., Gastaldelli, A., de Iasio, R., Gentilcore, E., Natale, S., Cassader, M., Rizzetto, M., et al (2005). Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity. J Clin Endocrinol Metab 90, 3498–3504. |
| [23] | Hui, J. M., Hodge, A., Farrell, G. C., Kench, J. G., Kriketos, A., and George, J (2004). Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40, 46–54. |
| [24] | Langin, D (2006). Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol Res. 53, 482–491. |
| [25] | Castillero, E., Isabel Martı´n, A., Paz Nieto-Bona1, M., Ferna´ndez-Galaz, C., Lo´ pez-Menduin,˜ M., A´ ngeles Villanu,´ M., and Lo´ pez-Caldero´n, A. (2012) Fenofibrate administration to arthritic rats increases adiponectin and leptin and prevents oxidative muscle wasting. Endocrine Connections. 01, 1–12. |
| [26] | Moncsek A., Al-Suraih M. S., Trussoni C. E., O'Hara S. P., Splinter P. L., Zuber C., Patsenker E., Valli P. V., Fingas C. D., Weber A., Zhu Y., Tchkonia T., Kirkland J. L., Gores G. J., Müllhaupt B., Nicholas F., LaRusso N. F., Mertens J. C. (2017) online. Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2−/−) mice Mertens. Hepatology. 67 (1), 247–259. |
| [27] | Hui-juan, L., Cheng-yu, Z., Fei, S., Ting, X., Jing, M., Qiang, Z., Cai-li Liang, S. L., Jing W., Zhang B., Yan-rong, L., Tao, S., and Zhou, H. G (2015). A Novel Partial Agonist of Peroxisome Proliferator-Activated Receptor γ with Excellent Effect on Insulin Resistance and Type 2 Diabetes. Journal of Pharmacology and Experimental Therapeutics 353 (3), 573-581. |
| [28] | Sanyal, A. J., Campbell-Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L. and Clore, J. N (2001). Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120, 1183–1192. |
| [29] | Chandra, S.. De K., Ganguly S., Sarkar B. and Misra M. (2009). Synthesis, radiolabeling and biological evaluation of a neutral tripeptide and its derivatives for potential nuclear medicine applications. Peptides 30, 2399–2408. |
| [30] | Ferré, P (2004). The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53, S43–S50. |
| [31] | Crespo, J., Cayón, A., Fernández-Gil, P., Hernández-Guerra, M., Mayorga, M., Domínguez-Díez, A., Fernández-Escalante, J. C. and Pons-Romero, F (2001). Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34, 1158–1163. |
| [32] | Haukeland, J. W., Damås, J. K., Konopski, Z., Løberg, E. M., Haaland, T., Goverud, I., Torjesen, P. A., Birkeland, K., Bjørob and K., Aukrust, P (2006). Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J Hepatol. 44, 1167–1174. |
| [33] | Klover, P. J., Zimmers, T. A., Koniaris, L. G., and Mooney, R. A (2003). Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52, 2784–2789. |
| [34] | Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E. and Ridker, P. M (2001). C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286, 327–334. |
| [35] | Raubenheimer, P. J., Nyirenda, M. J. and Walker, B. R (2006). A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet. Diabetes 55, 2015–2020. |
| [36] | Feldstein, A. E: Novel insights into the pathophysiology of nonalcoholic fatty liver disease (2010). Semin Liver Dis 30, 391–401. |
| [37] | Wieckowska, A., Papouchado, B. G., Li, Z., Lopez, R., Zein, N. N. and Feldstein, A. E (2008). Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 103, 1372–1379. |
| [38] | Jin, X., Zimmers, T. A., Perez, E. A., Pierce, R. H., Zhang, Z. and Koniaris, L. G (2006). Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. Hepatology 43, 474–484. |
| [39] | Miura, K., Yang, L., vanRooijen, N., Ohnishi, H. and Seki, E (2012). Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2. Am J Physiol Gastrointest Liver Physiol 302, G1310–G1321. |
| [40] | Brown, B. N., Ratner, B. D., Goodman, S. B., Amar, S. and Badylak, S. F (2012). Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 33, 3792–3802. |
APA Style
Susmita Chandra. (2018). Regulation of HepG2 Fat Metabolism by IL1β and IL1 Receptor Antagonist. Cancer Research Journal, 5(4), 24-34. https://doi.org/10.11648/j.crj.20170504.11
ACS Style
Susmita Chandra. Regulation of HepG2 Fat Metabolism by IL1β and IL1 Receptor Antagonist. Cancer Res. J. 2018, 5(4), 24-34. doi: 10.11648/j.crj.20170504.11
AMA Style
Susmita Chandra. Regulation of HepG2 Fat Metabolism by IL1β and IL1 Receptor Antagonist. Cancer Res J. 2018;5(4):24-34. doi: 10.11648/j.crj.20170504.11
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.crj.20170504.11,
author = {Susmita Chandra},
title = {Regulation of HepG2 Fat Metabolism by IL1β and IL1 Receptor Antagonist},
journal = {Cancer Research Journal},
volume = {5},
number = {4},
pages = {24-34},
doi = {10.11648/j.crj.20170504.11},
url = {https://doi.org/10.11648/j.crj.20170504.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20170504.11},
abstract = {Non-alcoholic fatty liver disease (NAFLD) is the major cause of steatohepatitis, cirrhosis and hepatocellular carcinoma. High saturated fat rich diet is one of the known causes of NAFLD. Non-Alcoholic liver disease NAFLD is characterized by steatosis and upregulation of different proinflammatory cytokines, like caspase-1 dependant IL1β, type I IL1 receptor (IL1R1), and IL1 receptor antagonist (IL1Ra). Till date there is no proper treatment option available for NASH except management of obesity and food intake. Anti inflammatory drugs are used as a treatment option in atherosclerosis, where inflammatory response plays an important role. Keeping a similarity in mind the recombinant IL1Ra and inflammatory cytokine IL1β was tested as treatmet option for high fat condition in Palmitate treated HepG2 cells. The lipid metabolism pathways were tested with a purchased recombinant product as well as with THP1 and its macrophage extracted product. The major outcome was removal of storage fat from the cells by increasing the beta oxidation level. So the conclusion was that IL1Ra can play a major role in controlling the accumulated fatty level in liver cells.},
year = {2018}
}
TY - JOUR T1 - Regulation of HepG2 Fat Metabolism by IL1β and IL1 Receptor Antagonist AU - Susmita Chandra Y1 - 2018/01/16 PY - 2018 N1 - https://doi.org/10.11648/j.crj.20170504.11 DO - 10.11648/j.crj.20170504.11 T2 - Cancer Research Journal JF - Cancer Research Journal JO - Cancer Research Journal SP - 24 EP - 34 PB - Science Publishing Group SN - 2330-8214 UR - https://doi.org/10.11648/j.crj.20170504.11 AB - Non-alcoholic fatty liver disease (NAFLD) is the major cause of steatohepatitis, cirrhosis and hepatocellular carcinoma. High saturated fat rich diet is one of the known causes of NAFLD. Non-Alcoholic liver disease NAFLD is characterized by steatosis and upregulation of different proinflammatory cytokines, like caspase-1 dependant IL1β, type I IL1 receptor (IL1R1), and IL1 receptor antagonist (IL1Ra). Till date there is no proper treatment option available for NASH except management of obesity and food intake. Anti inflammatory drugs are used as a treatment option in atherosclerosis, where inflammatory response plays an important role. Keeping a similarity in mind the recombinant IL1Ra and inflammatory cytokine IL1β was tested as treatmet option for high fat condition in Palmitate treated HepG2 cells. The lipid metabolism pathways were tested with a purchased recombinant product as well as with THP1 and its macrophage extracted product. The major outcome was removal of storage fat from the cells by increasing the beta oxidation level. So the conclusion was that IL1Ra can play a major role in controlling the accumulated fatty level in liver cells. VL - 5 IS - 4 ER -
Information
Email: