1. Younossi, ZM, Marchesini, G, Pinto-Cortez, H, Petta, S. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: implications for liver transplantation. Transplantation. 2019;103(1):22–7.
Google Scholar | Crossref2. Chalasani, N, Younossi, Z, Lavine, JE, Charlton, M, Cusi, K, Rinella, M, Harrison, SA, Brunt, EM, Sanyal, AJ. 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):328–57.
Google Scholar | Crossref3. Patterson, RE, Sears, DD. Metabolic effects of intermittent fasting. Annu Rev Nutr. 2017;37:371–93.
Google Scholar | Crossref4. Longo, VD, Mattson, MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181–92.
Google Scholar | Crossref5. Yang, W, Cao, M, Mao, X, Wei, X, Li, X, Chen, G, Zhang, J, Wang, Z, Shi, J, Huang, H, Yao, X, Liu, C. Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of toll-like receptor 4/nuclear factor kappaB signaling. Nutr Res. 2016;36(6):586–93. doi:10.1016/j.nutres.2016.02.001.
Google Scholar | Crossref6. DiNicolantonio, JJ, McCarty, M. Autophagy-induced degradation of Notch1, achieved through intermittent fasting, may promote beta cell neogenesis: implications for reversal of type 2 diabetes. Open Heart. 2019;6(1):e001028.
Google Scholar | Crossref7. Chen, J, Montagner, A, Tan, NS, Wahli, W. Insights into the Role of PPARβ/δ in NAFLD. Int J Mol Sci. 2018;19(7):1893.
Google Scholar | Crossref8. Kanda, T, Matsuoka, S, Yamazaki, M, Shibata, T, Nirei, K, Takahashi, H, Kaneko, T, Fujisawa, M, Higuchi, T, Nakamura, H. Apoptosis and non-alcoholic fatty liver diseases. World J Gastroenterol. 2018;24(25):2661.
Google Scholar | Crossref9. Ahmed, A, Saeed, F, Arshad, MU, Afzaal, M, Imran, A, Ali, SW, Niaz, B, Ahmad, A, Imran, M. Impact of intermittent fasting on human health: an extended review of metabolic cascades. Int J Food Prop. 2018;21(1):2700–13.
Google Scholar | Crossref10. Faul, F, Erdfelder, E, Buchner, A, Lang, AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41(4):1149–60.
Google Scholar | Crossref11. Choi, JH, Jin, SW, Choi, CY, Kim, HG, Kim, SJ, Lee, HS, Chung, YC, Kim, EJ, Lee, YC, Jeong, HG. Saponins from the roots of Platycodon grandiflorum ameliorate high fat diet-induced non-alcoholic steatohepatitis. Biomed Pharmacother. 2017;86:205–12. doi:10.1016/j.biopha.2016.11.107.
Google Scholar | Crossref12. Li, H, Ying, H, Hu, A, Hu, Y, Li, D. Therapeutic effect of gypenosides on nonalcoholic steatohepatitis via regulating hepatic lipogenesis and fatty acid oxidation. Biol Pharm Bull. 2017;40(5):650–7.
Google Scholar | Crossref13. Liu, XL, Ming, YN, Zhang, JY, Chen, XY, Zeng, MD, Mao, YM. Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes. Exp Mol Med. 2017;49(1):e283.
Google Scholar | Crossref14. Yang, XX, Wang, X, Shi, TT, Dong, JC, Li, FJ, Zeng, LX, Yang, M, Gu, W, Li, JP, Yu, J. Mitochondrial dysfunction in high-fat diet-induced nonalcoholic fatty liver disease: the alleviating effect and its mechanism of Polygonatum kingianum. Biomed Pharmacother. 2019;117:109083. doi:10.1016/j.biopha.2019.109083.
Google Scholar | Crossref15. Christensen, CU, Glavind, E, Thomsen, KL, Kim, YO, Heebøll, S, Schuppan, D, Hamilton-Dutoit, S, Würtz Heegaard, C, Grønbæk, H. Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease. PLOS ONE. 2018;13(3):e0192728. doi:10.1371/journal.pone.0192728.
Google Scholar | Crossref16. Sylvester Darvin, S, Toppo, E, Esakkimuthu, S, Ajeesh Krishna, TP, Ceasar, SA, Stalin, A, Balakrishna, K, Muniappan, N, Pazhanivel, N, Mahaprabhu, R, Paulraj, MG, Pandikumar, P, Ignacimuthu, S, Al-Dhabi, NA. Hepatoprotective effect of bisbenzylisoquinoline alkaloid tiliamosine from Tiliacora racemosa in high-fat diet/diethylnitrosamine-induced non-alcoholic steatohepatitis. Biomed Pharmacother. 2018;108:963–73. doi:10.1016/j.biopha.2018.09.116.
Google Scholar | Crossref17. Kucera, O, Cervinkova, Z. Experimental models of non-alcoholic fatty liver disease in rats. World J Gastroenterol. 2014;20(26):8364.
Google Scholar | Crossref18. Jensen, VS, Hvid, H, Damgaard, J, Nygaard, H, Ingvorsen, C, Wulff, EM, Lykkesfeldt, J, Fledelius, C. Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague-Dawley rats. Diabetol Metab Syndr. 2018;10:4. doi:10.1186/s13098-018-0307-8.
Google Scholar | Crossref19. Burtis, CA, Ashwood, ER. Tietz textbook of clinical chemistry. Philadelphia: W.B. Saunders; 1999. p. 1654–5.
Google Scholar20. Elsayed, HRH, Anbar, HS, Rabei, MR, Adel, M, El-Gamal, R. Eicosapentaenoic and docosahexaenoic acids attenuate methotrexate-induced apoptosis and suppression of splenic T, B-Lymphocytes and macrophages with modulation of expression of CD3, CD20 and CD68. Tissue and Cell. 2021;72:101533.
Google Scholar | Crossref21. Primer3 web . 2019 [cited 2019 July 5]. Available from: http://primer3.ut.ee
Google Scholar22. Primer- BLAST . 2019 [cited 2019 July 5]. Available from: https://www.ncbi.nlm.nih.gov/tools/primer-blast/
Google Scholar23. Livak, KJ, Schmittgen, TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta C(T)) Method. Methods. 2001;25(4):402–8.
Google Scholar | Crossref24. Layman, JI, Pereira, DL, Chellan, N, Huisamen, B, Kotzé, SH. A histomorphometric study on the hepatoprotective effects of a green rooibos extract in a diet-induced obese rat model. Acta Histochem. 2019;121(5):646–56.
Google Scholar | Crossref25. Bisen, PS . Laboratory protocols in applied life sciences. Hoboken: Taylor & Francis; 2014.
Google Scholar | Crossref26. Brunt, EM, Janney, CG, Di Bisceglie, AM, Neuschwander-Tetri, BA, Bacon, BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94(9):2467–74.
Google Scholar | Crossref27. Elsayed, HRH, El-Nablaway, M, Othman, BH, Abdalla, AM, El Nashar, EM, Abd-Elmonem, MM, El-Gamal, R. Can dasatinib ameliorate the hepatic changes, induced by long term western diet, in mice? Ann Anat. 2020;234:151626. doi:10.1016/j.aanat.2020.151626.
Google Scholar | Crossref28. Schneider, CA, Rasband, WS, Eliceiri, KW. NIH image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.
Google Scholar | Crossref | Medline29. Schindelin, J, Arganda-Carreras, I, Frise, E, Kaynig, V, Longair, M, Pietzsch, T, Preibisch, S, Rueden, C, Saalfeld, S, Schmid, B. Fiji: an open-source platform for biological-image analysis. Nature Method. 2012;9(7):676–82.
Google Scholar | Crossref30. Renaud, HJ, Cui, JY, Lu, H, Klaassen, CD. Effect of diet on expression of genes involved in lipid metabolism, oxidative stress, and inflammation in mouse liver–insights into mechanisms of hepatic steatosis. PLOS ONE. 2014;9(2):e88584.
Google Scholar | Crossref31. Fraulob, JC, Ogg-Diamantino, R, Fernandes-Santos, C, Aguila, MB, Mandarim-de-Lacerda, CA. A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL/6 mice fed a high fat diet. J Clin Biochem Nutr. 2010;46(3):212–23.
Google Scholar | Crossref32. Harvie, M, Howell, A. Potential benefits and harms of intermittent energy restriction and intermittent fasting amongst obese, overweight and normal weight subjects—a narrative review of human and animal evidence. Behav Sci. 2017;7(1):4.
Google Scholar | Crossref33. Elsayed, HRH, El Nashar, EM, Abd-Elmonem, MM. Is the hepatocyte ultrastructural zonal heterogeneity changed by overnight (16 h) fasting? Morphometric study. Ultrastruct Pathol. 2019;43(6):290–300.
Google Scholar | Crossref34. Jensen, T, Kiersgaard, M, Sørensen, D, Mikkelsen, L. Fasting of mice: a review. Lab Anim. 2013;47(4):225–40.
Google Scholar | SAGE Journals35. Wu, Y, Zhou, F, Jiang, H, Wang, Z, Hua, C, Zhang, Y. Chicory (Cichorium intybus L.) Polysaccharides attenuate high-fat diet induced non-alcoholic fatty liver disease via AMPK activation. Int J Biol Macromol. 2018;118(PtA): 886–95.
Google Scholar | Crossref36. Skat-Rordam, J, Hojland Ipsen, D, Lykkesfeldt, J, Tveden-Nyborg, P. A role of peroxisome proliferator-activated receptor gamma in non-alcoholic fatty liver disease. Basic Clin Pharmacol Toxicol. 2019;124(5):528–37.
Google Scholar | Crossref37. Matsusue, K, Haluzik, M, Lambert, G, Yim, S-H, Gavrilova, O, Ward, JM, Brewer, B, Reitman, ML, Gonzalez, FJ. Liver-specific disruption of PPARγ in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Invest. 2003;111(5):737–47.
Google Scholar | Crossref38. Rotman, Y, Sanyal, AJ. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut. 2017;66(1):180–90.
Google Scholar | Crossref39. Wang, Y, Botolin, D, Xu, J, Christian, B, Mitchell, E, Jayaprakasam, B, Nair, MG, Peters, JM, Busik, JV, Olson, LK, Jump, DB. Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity. J Lipid Res. 2006;47(9):2028–41. doi:10.1194/jlr.M600177-JLR200.
Google Scholar | Crossref40. Wang, Y, Botolin, D, Christian, B, Busik, J, Xu, J, Jump, DB. Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases. J Lipid Res. 2005;46(4):706–15.
Google Scholar | Crossref41. Jump, DB . N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr Opin Lipidol. 2008;19(3):242–7.
Google Scholar | Crossref42. Unger, RH, Scherer, PE. Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab. 2010;21(6):345–52.
Google Scholar | Crossref43. Mao, J, DeMayo, FJ, Li, H, Abu-Elheiga, L, Gu, Z, Shaikenov, TE, Kordari, P, Chirala, SS, Heird, WC, Wakil, SJ. Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc Natl Acad Sci USA. 2006;103(22):8552–7. doi:10.1073/pnas.0603115103.
Google Scholar | Crossref44. Savage, DB, Choi, CS, Samuel, VT, Liu, ZX, Zhang, D, Wang, A, Zhang, XM, Cline, GW, Yu, XX, Geisler, JG, Bhanot, S, Monia, BP, Shulman, GI. Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest. 2006;116(3):817–24. doi:10.1172/JCI27300.
Google Scholar | Crossref45. Cave, MC, Clair, HB, Hardesty, JE, Falkner, KC, Feng, W, Clark, BJ, Sidey, J, Shi, H, Aqel, BA, McClain, CJ. Nuclear receptors and nonalcoholic fatty liver disease. Biochim Biophys Acta. 2016;1859(9):1083–99.
Google Scholar46. Berghe, WV, Vermeulen, L, Delerive, P, De Bosscher, K, Staels, B, Haegeman, G. A paradigm for gene regulation: inflammation, NF-κB and PPAR. Adv Exp Med Biol. 2003;544:181–96.
Google Scholar | Crossref47. Patsouris, D, Reddy, JK, Müller, M, Kersten, S. Peroxisome proliferator-activated receptor α mediates the effects of high-fat diet on hepatic gene expression. Endocrinology. 2006;147(3):1508–16.
Google Scholar | Crossref48. Pawlak, M, Lefebvre, P, Staels, B. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2015;62(3):720–33.
Google Scholar | Crossref49. Ratziu, V, Harrison, SA, Francque, S, Bedossa, P, Lehert, P, Serfaty, L, Romero-Gomez, M, Boursier, J, Abdelmalek, M, Caldwell, S. Elafibranor, an agonist of the peroxisome proliferator− activated receptor− α and− δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150(5):1147–59.
Google Scholar | Crossref50. Fernández-Miranda, C, Pérez-Carreras, M, Colina, F, López-Alonso, G, Vargas, C, Solís-Herruzo, JA. A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis. 2008;40(3):200–5.
Google Scholar | Crossref51. Yan, F, Wang, Q, Xu, C, Cao, M, Zhou, X, Wang, T, Yu, C, Jing, F, Chen, W, Gao, L. Peroxisome proliferator-activated receptor α activation induces hepatic steatosis, suggesting an adverse effect. PLOS ONE. 2014;9(6):e99245.
Google Scholar | Crossref52. Jin, S, Dai, C-L. Attenuation of reperfusion-induced hepatocyte apoptosis is associated with reversed bcl-2/bax ratio in hemi-hepatic artery-preserved portal occlusion. J Surg Res. 2012;174(2):298–304.
Google Scholar | Crossref53. Mattson, MP, Camandola, S. NF-κB in neuronal plasticity and neurodegenerative disorders. J Clin Invest. 2001;107(3):247–54.
Google Scholar | Crossref54. Ramalho, RM, Cortez-Pinto, H, Castro, RE, Solá, S, Costa, A, Moura, MC, Camilo, ME, Rodrigues, CM. Apoptosis and Bcl-2 expression in the livers of patients with steatohepatitis. Eur J Gastroenterol Hepatol. 2006;18(1):21–9. doi:10.1097/00042737-200601000.
Google Scholar | Crossref55. Yadav, SS, Sindram, D, Perry, DK, Clavien, PA. Ischemic preconditioning protects the mouse liver by inhibition of apoptosis through a caspase-dependent pathway. Hepatology. 1999;30(5):1223–31.
Google Scholar | Crossref56. Circu, ML, Aw, TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48(6):749–62.
Google Scholar | Crossref57. Perry, DK, Smyth, MJ, Stennicke, HR, Salvesen, GS, Duriez, P, Poirier, GG, Hannun, YA. Zinc is a potent inhibitor of the apoptotic protease, caspase-3 a novel target for zinc in the inhibition of apoptosis. J Biol Chem. 1997;272(30):18530–3.
Google Scholar |