Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

Metabolism: Clinical and Experimental

Volumn 65, Issue 8, 2016, Pages 1049-1061

  Mota, Manoela ^a   Banini, Bubu A ^a   Cazanave, Sophie C ^a   Sanyal, Arun J ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

CHOP; JNK; Lipid; NASH; Oxidative stress

Indexed keywords

BH3 PROTEIN; BILE ACID; BIM PROTEIN; CARBOHYDRATE; CASPASE; CCAAT ENHANCER BINDING PROTEIN; CERAMIDE; CHOLESTEROL; DEATH RECEPTOR; FRUCTOSE; GLUCOSE; LIPID; LYSOPHOSPHATIDYLCHOLINE; MITOGEN ACTIVATED PROTEIN KINASE; MONOUNSATURATED FATTY ACID; POLYUNSATURATED FATTY ACID; PROTEIN C JUN; PUMA PROTEIN; TRIACYLGLYCEROL; DDIT3 PROTEIN, HUMAN; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; STRESS ACTIVATED PROTEIN KINASE;

ARTICLE; ENDOPLASMIC RETICULUM STRESS; GLUCOSE INTAKE; GLUCOSE TRANSPORT; GLUCOTOXICITY; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; LIPOGENESIS; LIPOTOXICITY; LIVER CELL; LIVER CELL DAMAGE; MITOCHONDRION; NONALCOHOLIC FATTY LIVER; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; UPREGULATION; GLUCOSE INTOLERANCE; INSULIN RESISTANCE; METABOLISM; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ENDOPLASMIC RETICULUM STRESS; GLUCOSE INTOLERANCE; HUMANS; INSULIN RESISTANCE; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MITOCHONDRIA; NON-ALCOHOLIC FATTY LIVER DISEASE; OXIDATIVE STRESS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR CHOP;

EID: 84961226602     PISSN: 00260495     EISSN: 15328600     Source Type: Journal    
DOI: 10.1016/j.metabol.2016.02.014     Document Type: Article

References (123)

1. [1] Donnelly, K.L., Smith, C.I., Schwarzenberg, S.J., Jessurun, J., Boldt, M.D., Parks, E.J., Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:5 (2005), 1343–1351, 10.1172/JCI23621.
2. [2] Stremmel, W., Staffer, S., Wannhoff, A., Pathil, A., Chamulitrat, W., Plasma membrane phospholipase A2 controls hepatocellular fatty acid uptake and is responsive to pharmacological modulation: implications for nonalcoholic steatohepatitis. FASEB J 28:7 (2014), 3159–3170, 10.1096/fj.14-249763.
3. [3] Pan, X., Wang, P., Luo, J., et al. Adipogenic changes of hepatocytes in a high-fat diet-induced fatty liver mice model and non-alcoholic fatty liver disease patients. Endocrine 48:3 (2015), 834–847, 10.1007/s12020-014-0384-x.
4. [4] Chabowski, A., Zendzian-Piotrowska, M., Konstantynowicz, K., et al. Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes. Acta Physiol (Oxf) 207:2 (2013), 346–357, 10.1111/apha.12022.
5. [5] Lewis, G.F., Carpentier, A., Adeli, K., Giacca, A., Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23:2 (2002), 201–229, 10.1210/edrv.23.2.0461.
6. [6] Cambri, L.T., Ghezzi, A.C., Arsa, G., Botezelli, J.D., de Mello, M.A., Standard short-term diet ameliorates the lipid profile altered by a fructose-rich diet in rats. J Dev Orig Health Dis 6:4 (2015), 335–341, 10.1017/S2040174415001026.
7. [7] Ricchi, M., Odoardi, M.R., Carulli, L., et al. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol 24:5 (2009), 830–840, 10.1111/j.1440-1746.2008.05733.x.
8. [8] Listenberger, L.L., Han, X., Lewis, S.E., et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A 100:6 (2003), 3077–3082, 10.1073/pnas.0630588100.
9. [9] Yamaguchi, K., Yang, L., McCall, S., et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45:6 (2007), 1366–1374, 10.1002/hep.21655.
10. [10] Lauber, K., Bohn, E., Krober, S.M., et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:6 (2003), 717–730 [doi: S0092867403004227, pii].
11. [11] Han, M.S., Park, S.Y., Shinzawa, K., et al. Lysophosphatidylcholine as a death effector in the lipoapoptosis of hepatocytes. J Lipid Res 49:1 (2008), 84–97 [doi: M700184-JLR200, pii].
12. [12] Yaligar, J., Gopalan, V., Kiat, O.W., et al. Evaluation of dietary effects on hepatic lipids in high fat and placebo diet fed rats by in vivo MRS and LC–MS techniques. PLoS One, 9(3), 2014, e91436, 10.1371/journal.pone.0091436.
13. [13] Pathil, A., Mueller, J., Warth, A., Chamulitrat, W., Stremmel, W., Ursodeoxycholyl lysophosphatidylethanolamide improves steatosis and inflammation in murine models of nonalcoholic fatty liver disease. Hepatology 55:5 (2012), 1369–1378, 10.1002/hep.25531.
14. [14] Kakisaka, K., Cazanave, S.C., Fingas, C.D., et al. Mechanisms of lysophosphatidylcholine-induced hepatocyte lipoapoptosis. Am J Physiol Gastrointest Liver Physiol 302:1 (2012), G77–G84, 10.1152/ajpgi.00301.2011.
15. [15] Chavez, J.A., Siddique, M.M., Wang, S.T., Ching, J., Shayman, J.A., Summers, S.A., Ceramides and glucosylceramides are independent antagonists of insulin signaling. J Biol Chem 289:2 (2014), 723–734, 10.1074/jbc.M113.522847.
16. [16] Anjani, K., Lhomme, M., Sokolovska, N., et al. Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity. J Hepatol 62:4 (2015), 905–912, 10.1016/j.jhep.2014.11.002.
17. [17] Pagadala, M., Kasumov, T., McCullough, A.J., Zein, N.N., Kirwan, J.P., Role of ceramides in nonalcoholic fatty liver disease. Trends Endocrinol Metab 23:8 (2012), 365–371, 10.1016/j.tem.2012.04.005.
18. [18] Schwabe, R.F., Brenner, D.A., Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol 290:4 (2006), G583–G589 [doi: 290/4/G583, pii].
19. [19] Longato, L., Tong, M., Wands, J.R., de la Monte, S.M., High fat diet induced hepatic steatosis and insulin resistance: role of dysregulated ceramide metabolism. Hepatol Res 42:4 (2012), 412–427, 10.1111/j.1872-034X.2011.00934.x.
20. [20] Kasumov, T., Li, L., Li, M., et al. Ceramide as a mediator of non-alcoholic fatty liver disease and associated atherosclerosis. PLoS One, 10(5), 2015, e0126910, 10.1371/journal.pone.0126910.
21. [21] Konstantynowicz-Nowicka, K., Harasim, E., Baranowski, M., Chabowski, A., New evidence for the role of ceramide in the development of hepatic insulin resistance. PLoS One, 10(1), 2015, e0116858, 10.1371/journal.pone.0116858.
22. [22] Wei, Y., Wang, D., Topczewski, F., Pagliassotti, M.J., Saturated fatty acids induce endoplasmic reticulum sress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 291:2 (2006), E275–E281 [doi: 00644.2005, pii].
23. [23] Feldstein, A.E., Werneburg, N.W., Li, Z., Bronk, S.F., Gores, G.J., Bax inhibition protects against free fatty acid-induced lysosomal permeabilization. Am J Physiol Gastrointest Liver Physiol 290:6 (2006), G1339–G1346 [doi: 00509.2005, pii].
24. [24] Janikiewicz, J., Hanzelka, K., Kozinski, K., Kolczynska, K., Dobrzyn, A., Islet beta-cell failure in type 2 diabetes–within the network of toxic lipids. Biochem Biophys Res Commun 460:3 (2015), 491–496, 10.1016/j.bbrc.2015.03.153.
25. [25] Kurek, K., Piotrowska, D.M., Wiesiolek-Kurek, P., et al. Inhibition of ceramide de novo synthesis reduces liver lipid accumulation in rats with nonalcoholic fatty liver disease. Liver Int 34:7 (2014), 1074–1083, 10.1111/liv.12331.
26. [26] Babenko, N.A., Kharchenko, V.S., Effects of inhibitors of key enzymes of sphingolipid metabolism on insulin-induced glucose uptake and glycogen synthesis in liver cells of old rats. Biochemistry (Mosc) 80:1 (2015), 104–112, 10.1134/S0006297915010125.
27. [27] Arguello, G., Balboa, E., Arrese, M., Zanlungo, S., Recent insights on the role of cholesterol in non-alcoholic fatty liver disease. Biochim Biophys Acta 1852:9 (2015), 1765–1778, 10.1016/j.bbadis.2015.05.015.
28. [28] Caballero, F., Fernandez, A., De Lacy, A.M., Fernandez-Checa, J.C., Caballeria, J., Garcia-Ruiz, C., Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J Hepatol 50:4 (2009), 789–796, 10.1016/j.jhep.2008.12.016.
29. [29] Bellanti, F., Mitarotonda, D., Tamborra, R., et al. Oxysterols induce mitochondrial impairment and hepatocellular toxicity in non-alcoholic fatty liver disease. Free Radic Biol Med 75:Suppl. 1 (2014), S16–S17, 10.1016/j.freeradbiomed.2014.10.594.
30. [30] Liang, T., Alloosh, M., Bell, L.N., et al. Liver injury and fibrosis induced by dietary challenge in the ossabaw miniature swine. PLoS One, 10(5), 2015, e0124173, 10.1371/journal.pone.0124173.
31. [31] Gan, L.T., Van Rooyen, D.M., Koina, M.E., McCuskey, R.S., Teoh, N.C., Farrell, G.C., Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol 61:6 (2014), 1376–1384, 10.1016/j.jhep.2014.07.024.
32. [32] Dongiovanni, P., Petta, S., Mannisto, V., et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol 63:3 (2015), 705–712, 10.1016/j.jhep.2015.05.006.
33. [33] Chong, L.W., Hsu, Y.C., Lee, T.F., et al. Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells. BMC Gastroenterol, 15, 2015, 22, 10.1186/s12876-015-0248-8.
34. [34] Ferreira, D.M., Afonso, M.B., Rodrigues, P.M., et al. C-jun N-terminal kinase 1/c-jun activation of the p53/microRNA 34a/sirtuin 1 pathway contributes to apoptosis induced by deoxycholic acid in rat liver. Mol Cell Biol 34:6 (2014), 1100–1120, 10.1128/MCB.00420-13.
35. [35] Ali, A.H., Carey, E.J., Lindor, K.D., Recent advances in the development of farnesoid X receptor agonists. Ann Transl Med, 3(1), 2015, 5, 10.3978/j.issn.2305-5839.2014.12.06.
36. [36] Bechmann, L.P., Kocabayoglu, P., Sowa, J.P., et al. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology 57:4 (2013), 1394–1406, 10.1002/hep.26225.
37. [37] Puri, P., Mirshahi, F., Cheung, O., et al. Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology 134:2 (2008), 568–576 [doi: S0016-5085(07)01919-1, pii].
38. [38] Szegezdi, E., Logue, S.E., Gorman, A.M., Samali, A., Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7:9 (2006), 880–885 [doi: 7400779, pii].
39. [39] Volmer, R., van der Ploeg, K., Ron, D., Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc Natl Acad Sci U S A 110:12 (2013), 4628–4633, 10.1073/pnas.1217611110.
40. [40] Shen, X., Ellis, R.E., Sakaki, K., Kaufman, R.J., Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genet, 1(3), 2005, e37, 10.1371/journal.pgen.0010037.
41. [41] Pardo, V., Gonzalez-Rodriguez, A., Muntane, J., Kozma, S.C., Valverde, A.M., Role of hepatocyte S6K1 in palmitic acid-induced endoplasmic reticulum stress, lipotoxicity, insulin resistance and in oleic acid-induced protection. Food Chem Toxicol 80 (2015), 298–309, 10.1016/j.fct.2015.03.029.
42. [42] Szegezdi, E., Macdonald, D.C., Ni Chonghaile, T., Gupta, S., Samali, A., Bcl-2 family on guard at the ER. Am J Physiol Cell Physiol 296:5 (2009), C941–C953, 10.1152/ajpcell.00612.2008.
43. [43] Rutkowski, D.T., Wu, J., Back, S.H., et al. UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Dev Cell 15:6 (2008), 829–840, 10.1016/j.devcel.2008.10.015.
44. [44] Lee, A.H., Scapa, E.F., Cohen, D.E., Glimcher, L.H., Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320:5882 (2008), 1492–1496, 10.1126/science.1158042.
45. [45] Oyadomari, S., Harding, H.P., Zhang, Y., Oyadomari, M., Ron, D., Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab 7:6 (2008), 520–532, 10.1016/j.cmet.2008.04.011.
46. [46] Lake, A.D., Novak, P., Hardwick, R.N., et al. The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease. Toxicol Sci 137:1 (2014), 26–35, 10.1093/toxsci/kft230.
47. [47] Teske, B.F., Wek, S.A., Bunpo, P., et al. The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress. Mol Biol Cell 22:22 (2011), 4390–4405, 10.1091/mbc.E11-06-0510.
48. [48] Pfaffenbach, K.T., Gentile, C.L., Nivala, A.M., Wang, D., Wei, Y., Pagliassotti, M.J., Linking endoplasmic reticulum stress to cell death in hepatocytes: roles of C/EBP homologous protein and chemical chaperones in palmitate-mediated cell death. Am J Physiol Endocrinol Metab 298:5 (2010), E1027–E1035, 10.1152/ajpendo.00642.2009.
49. [49] Zhang, J., Singh, N., Robinson-Taylor, K.S., et al. Hepatocyte autophagy is linked to C/EBP-homologous protein, Bcl2-interacting mediator of cell death, and BH3-interacting domain death agonist gene expression. J Surg Res 195:2 (2015), 588–595, 10.1016/j.jss.2015.01.039.
50. [50] Cazanave, S.C., Elmi, N.A., Akazawa, Y., Bronk, S.F., Mott, J.L., Gores, G.J., CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis. Am J Physiol Gastrointest Liver Physiol 299:1 (2010), G236–G243, 10.1152/ajpgi.00091.2010.
51. [51] Iurlaro, R., Munoz-Pinedo, C., Cell death induced by endoplasmic reticulum stress. FEBS J, 2015, 10.1111/febs.13598.
52. [52] Cazanave, S.C., Mott, J.L., Bronk, S.F., et al. Death receptor 5 signaling promotes hepatocyte lipoapoptosis. J Biol Chem 286:45 (2011), 39336–39348, 10.1074/jbc.M111.280420.
53. [53] Leamy, A.K., Egnatchik, R.A., Young, J.D., Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res 52:1 (2013), 165–174, 10.1016/j.plipres.2012.10.004.
54. [54] Malhi, H., Bronk, S.F., Werneburg, N.W., Gores, G.J., Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem 281:17 (2006), 12093–12101 [doi: M510660200, pii].
55. [55] Cazanave, S.C., Mott, J.L., Elmi, N.A., et al. JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis. J Biol Chem 284:39 (2009), 26591–26602, 10.1074/jbc.M109.022491.
56. [56] Pagliassotti, M.J., Wei, Y., Wang, D., Insulin protects liver cells from saturated fatty acid-induced apoptosis via inhibition of c-jun NH2 terminal kinase activity. Endocrinology 148:7 (2007), 3338–3345 [doi: en.2006-1710, pii].
57. [57] Hikita, H., Takehara, T., Kodama, T., et al. Delayed-onset caspase-dependent massive hepatocyte apoptosis upon fas activation in bak/bax-deficient mice. Hepatology 54:1 (2011), 240–251, 10.1002/hep.24305.
58. [58] Barreyro, F.J., Kobayashi, S., Bronk, S.F., Werneburg, N.W., Malhi, H., Gores, G.J., Transcriptional regulation of bim by FoxO3A mediates hepatocyte lipoapoptosis. J Biol Chem 282:37 (2007), 27141–27154 [doi: M704391200, pii].
59. [59] Masuoka, H.C., Mott, J., Bronk, S.F., et al. Mcl-1 degradation during hepatocyte lipoapoptosis. J Biol Chem 284:44 (2009), 30039–30048, 10.1074/jbc.M109.039545.
60. [60] Czabotar, P.E., Lessene, G., Strasser, A., Adams, J.M., Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 15:1 (2014), 49–63, 10.1038/nrm3722.
61. [61] Eguchi, A., Wree, A., Feldstein, A.E., Biomarkers of liver cell death. J Hepatol 60:5 (2014), 1063–1074, 10.1016/j.jhep.2013.12.026.
62. [62] Thapaliya, S., Wree, A., Povero, D., et al. Caspase 3 inactivation protects against hepatic cell death and ameliorates fibrogenesis in a diet-induced NASH model. Dig Dis Sci 59:6 (2014), 1197–1206, 10.1007/s10620-014-3167-6.
63. [63] Heo, S.H., Kwak, J., Jang, K.L., All-trans retinoic acid induces p53-depenent apoptosis in human hepatocytes by activating p14 expression via promoter hypomethylation. Cancer Lett 362:1 (2015), 139–148, 10.1016/j.canlet.2015.03.036.
64. [64] Ratziu, V., Sheikh, M.Y., Sanyal, A.J., et al. A phase 2, randomized, double-blind, placebo-controlled study of GS-9450 in subjects with nonalcoholic steatohepatitis. Hepatology 55:2 (2012), 419–428, 10.1002/hep.24747.
65. [65] Malhi, H., Barreyro, F.J., Isomoto, H., Bronk, S.F., Gores, G.J., Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut 56:8 (2007), 1124–1131 [doi: gut.2006.118059, pii].
66. [66] Sanyal, A.J., Campbell-Sargent, C., Mirshahi, F., et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120:5 (2001), 1183–1192, 10.1053/gast.2001.23256.
67. [67] Koliaki, C., Szendroedi, J., Kaul, K., et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab 21:5 (2015), 739–746, 10.1016/j.cmet.2015.04.004.
68. [68] Park, E.J., Lee, A.Y., Chang, S.H., Yu, K.N., Kim, J.H., Cho, M.H., Role of p53 in the cellular response following oleic acid accumulation in chang liver cells. Toxicol Lett 224:1 (2014), 114–120, 10.1016/j.toxlet.2013.09.018.
69. [69] Martel, C., Allouche, M., Esposti, D.D., et al. Glycogen synthase kinase 3-mediated voltage-dependent anion channel phosphorylation controls outer mitochondrial membrane permeability during lipid accumulation. Hepatology 57:1 (2013), 93–102, 10.1002/hep.25967.
70. [70] Win, S., Than, T.A., Le, B.H., Garcia-Ruiz, C., Fernandez-Checa, J.C., Kaplowitz, N., Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity. J Hepatol 62:6 (2015), 1367–1374, 10.1016/j.jhep.2015.01.032.
71. [71] Penke, M., Larsen, P.S., Schuster, S., et al. Hepatic NAD salvage pathway is enhanced in mice on a high-fat diet. Mol Cell Endocrinol 412 (2015), 65–72, 10.1016/j.mce.2015.05.028.
72. [72] Gariani, K., Menzies, K.J., Ryu, D., et al. Eliciting the mitochondrial unfolded protein response via NAD repletion reverses fatty liver disease. Hepatology, 2015, 10.1002/hep.28245.
73. [73] Feldstein, A.E., Werneburg, N.W., Canbay, A., et al. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology 40:1 (2004), 185–194, 10.1002/hep.20283.
74. [74] Li, Z., Berk, M., McIntyre, T.M., Gores, G.J., Feldstein, A.E., The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity. Hepatology 47:5 (2008), 1495–1503, 10.1002/hep.22183.
75. [75] Egnatchik, R.A., Leamy, A.K., Noguchi, Y., Shiota, M., Young, J.D., Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes. Metabolism 63:2 (2014), 283–295, 10.1016/j.metabol.2013.10.009.
76. [76] Abdelmegeed, M.A., Banerjee, A., Yoo, S.H., Jang, S., Gonzalez, F.J., Song, B.J., Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis. J Hepatol 57:4 (2012), 860–866, 10.1016/j.jhep.2012.05.019.
77. [77] Aubert, J., Begriche, K., Knockaert, L., Robin, M.A., Fromenty, B., Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol 35:10 (2011), 630–637, 10.1016/j.clinre.2011.04.015.
78. [78] Lee, H.S., Daniels, B.H., Salas, E., Bollen, A.W., Debnath, J., Margeta, M., Clinical utility of LC3 and p62 immunohistochemistry in diagnosis of drug-induced autophagic vacuolar myopathies: A case–control study. PLoS One, 7(4), 2012, e36221, 10.1371/journal.pone.0036221.
79. [79] Lin, X., Li, S., Zhao, Y., et al. Interaction domains of p62: A bridge between p62 and selective autophagy. DNA Cell Biol 32:5 (2013), 220–227, 10.1089/dna.2012.1915.
80. [80] Cazanave, S.C., Wang, X., Zhou, H., et al. Degradation of Keap1 activates BH3-only proteins bim and PUMA during hepatocyte lipoapoptosis. Cell Death Differ 21:8 (2014), 1303–1312, 10.1038/cdd.2014.49.
81. [81] Sanyal, A.J., Chalasani, N., Kowdley, K.V., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362:18 (2010), 1675–1685, 10.1056/NEJMoa0907929.
82. [82] Lavine, J.E., Schwimmer, J.B., Van Natta, M.L., et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 305:16 (2011), 1659–1668, 10.1001/jama.2011.520.
83. [83] Li, L., Lu, D.Z., Li, Y.M., Zhang, X.Q., Zhou, X.X., Jin, X., Proteomic analysis of liver mitochondria from rats with nonalcoholic steatohepatitis. World J Gastroenterol 20:16 (2014), 4778–4786, 10.3748/wjg.v20.i16.4778.
84. [84] Li, Z.Z., Berk, M., McIntyre, T.M., Feldstein, A.E., Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 284:9 (2009), 5637–5644, 10.1074/jbc.M807616200.
85. [85] Akazawa, Y., Cazanave, S., Mott, J.L., et al. Palmitoleate attenuates palmitate-induced bim and PUMA up-regulation and hepatocyte lipoapoptosis. J Hepatol 52:4 (2010), 586–593, 10.1016/j.jhep.2010.01.003.
86. [86] El-Badry, A.M., Graf, R., Clavien, P.A., Omega 3 - omega 6: what is right for the liver?. J Hepatol 47:5 (2007), 718–725 [doi: S0168-8278(07)00466-7, pii].
87. [87] Puri, P., Baillie, R.A., Wiest, M.M., et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 46:4 (2007), 1081–1090, 10.1002/hep.21763.
88. [88] Videla, L.A., Rodrigo, R., Araya, J., Poniachik, J., Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic Biol Med 37:9 (2004), 1499–1507, 10.1016/j.freeradbiomed.2004.06.033.
89. [89] Nogueira, M.A., Oliveira, C.P., Ferreira Alves, V.A., et al. Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial. Clin Nutr, 2015 [doi: S0261-5614(15)00131-4, pii].
90. [90] Tanaka, N., Sano, K., Horiuchi, A., Tanaka, E., Kiyosawa, K., Aoyama, T., Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol 42:4 (2008), 413–418, 10.1097/MCG.0b013e31815591aa.
91. [91] Maruyama, H., Takahashi, M., Sekimoto, T., Shimada, T., Yokosuka, O., Linoleate appears to protect against palmitate-induced inflammation in Huh7 cells. Lipids Health Dis, 13, 2014, 78, 10.1186/1476-511X-13-78.
92. [92] Zhang, Y., Yang, X., Shi, H., Dong, L., Bai, J., Effect of alpha-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes. Lipids Health Dis, 10, 2011, 122, 10.1186/1476-511X-10-122.
93. [93] Sanyal, A.J., Abdelmalek, M.F., Suzuki, A., Cummings, O.W., Chojkier, M., EPE-A Study Group, No significant effects of Ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology 147:2 (2014), 377–384.e1, 10.1053/j.gastro.2014.04.046.
94. [94] Basaranoglu, M., Basaranoglu, G., Bugianesi, E., Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction. Hepatobiliary Surg Nutr 4:2 (2015), 109–116, 10.3978/j.issn.2304-3881.2014.11.05.
95. [95] Du, D., Shi, Y.H., Le, G.W., Oxidative stress induced by high-glucose diet in liver of C57BL/6 J mice and its underlying mechanism. Mol Biol Rep 37:8 (2010), 3833–3839, 10.1007/s11033-010-0039-9.
96. [96] Lim, J.S., Mietus-Snyder, M., Valente, A., Schwarz, J.M., Lustig, R.H., The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol 7:5 (2010), 251–264, 10.1038/nrgastro.2010.41.
97. [97] Janevski, M., Ratnayake, S., Siljanovski, S., McGlynn, M.A., Cameron-Smith, D., Lewandowski, P., Fructose containing sugars modulate mRNA of lipogenic genes ACC and FAS and protein levels of transcription factors ChREBP and SREBP1c with no effect on body weight or liver fat. Food Funct 3:2 (2012), 141–149, 10.1039/c1fo10111k.
98. [98] Maslak, E., Buczek, E., Szumny, A., et al. Individual CLA isomers, c9t11 and t10c12, prevent excess liver glycogen storage and inhibit lipogenic genes expression induced by high-fructose diet in rats. Biomed Res Int, 2015, 2015, 535982, 10.1155/2015/535982.
99. [99] Pagliassotti, M.J., Prach, P.A., Koppenhafer, T.A., Pan, D.A., Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol 271:5 Pt 2 (1996), R1319–R1326.
100. [100] Thresher, J.S., Podolin, D.A., Wei, Y., Mazzeo, R.S., Pagliassotti, M.J., Comparison of the effects of sucrose and fructose on insulin action and glucose tolerance. Am J Physiol Regul Integr Comp Physiol 279:4 (2000), R1334–R1340.
101. [101] Bezerra, R.M., Ueno, M., Silva, M.S., Tavares, D.Q., Carvalho, C.R., Saad, M.J., A high fructose diet affects the early steps of insulin action in muscle and liver of rats. J Nutr 130:6 (2000), 1531–1535.
102. [102] Rebollo, A., Roglans, N., Baena, M., et al. Liquid fructose down-regulates liver insulin receptor substrate 2 and gluconeogenic enzymes by modifying nutrient sensing factors in rats. J Nutr Biochem 25:2 (2014), 250–258, 10.1016/j.jnutbio.2013.10.014.
103. [103] Mozzini, C., Garbin, U., Stranieri, C., et al. Endoplasmic reticulum stress and Nrf2 repression in circulating cells of type 2 diabetic patients without the recommended glycemic goals. Free Radic Res 49:3 (2015), 244–252, 10.3109/10715762.2014.997229.
104. [104] Kunde, S.S., Roede, J.R., Vos, M.B., et al. Hepatic oxidative stress in fructose-induced fatty liver is not caused by sulfur amino acid insufficiency. Nutrients 3:11 (2011), 987–1002, 10.3390/nu3110987.
105. [105] Pooranaperundevi, M., Sumiyabanu, M.S., Viswanathan, P., Sundarapandiyan, R., Anuradha, C.V., Insulin resistance induced by high-fructose diet potentiates carbon tetrachloride hepatotoxicity. Toxicol Ind Health 26:2 (2010), 89–104, 10.1177/0748233709359273.
106. [106] Sivaraman, K., Senthilkumar, G.P., Sankar, P., Bobby, Z., Attenuation of oxidative stress, inflammation and insulin resistance by Allium sativum in fructose-fed male rats. J Clin Diagn Res 7:9 (2013), 1860–1862, 10.7860/JCDR/2013/6924.3334.
107. [107] Wei, Y., Pagliassotti, M.J., Hepatospecific effects of fructose on c-jun NH2-terminal kinase: implications for hepatic insulin resistance. Am J Physiol Endocrinol Metab 287:5 (2004), E926–E933, 10.1152/ajpendo.00185.2004.
108. [108] Pang, J., Gong, H., Xi, C., Fan, W., Dai, Y., Zhang, T.M., Poly(ADP-ribose) polymerase 1 is involved in glucose toxicity through SIRT1 modulation in HepG2 hepatocytes. J Cell Biochem 112:1 (2011), 299–306, 10.1002/jcb.22919.
109. [109] Sodhi, K., Puri, N., Favero, G., et al. Fructose mediated non-alcoholic fatty liver is attenuated by HO-1-SIRT1 module in murine hepatocytes and mice fed a high fructose diet. PLoS One, 10(6), 2015, e0128648, 10.1371/journal.pone.0128648.
110. [110] Liu, X., Gao, Y., Li, M., et al. Sirt1 mediates the effect of the heme oxygenase inducer, cobalt protoporphyrin, on ameliorating liver metabolic damage caused by a high-fat diet. J Hepatol, 2015 [doi: S0168-8278(15)00345-1, pii].
111. [111] Agouni, A., Mody, N., Owen, C., et al. Liver-specific deletion of protein tyrosine phosphatase (PTP) 1B improves obesity- and pharmacologically induced endoplasmic reticulum stress. Biochem J 438:2 (2011), 369–378, 10.1042/BJ20110373.
112. [112] Vasiljevic, A., Bursac, B., Djordjevic, A., et al. Hepatic inflammation induced by high-fructose diet is associated with altered 11betaHSD1 expression in the liver of wistar rats. Eur J Nutr 53:6 (2014), 1393–1402, 10.1007/s00394-013-0641-4.
113. [113] Kanety, H., Feinstein, R., Papa, M.Z., Hemi, R., Karasik, A., Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. J Biol Chem 270:40 (1995), 23780–23784.
114. [114] Basaranoglu, M., Basaranoglu, G., Sabuncu, T., Senturk, H., Fructose as a key player in the development of fatty liver disease. World J Gastroenterol 19:8 (2013), 1166–1172, 10.3748/wjg.v19.i8.1166.
115. [115] Vila, L., Roglans, N., Alegret, M., Sanchez, R.M., Vazquez-Carrera, M., Laguna, J.C., Suppressor of cytokine signaling-3 (SOCS-3) and a deficit of serine/threonine (ser/thr) phosphoproteins involved in leptin transduction mediate the effect of fructose on rat liver lipid metabolism. Hepatology 48:5 (2008), 1506–1516, 10.1002/hep.22523.
116. [116] Ye, J., Zheng, R., Wang, Q., et al. Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth. Pediatr Res 72:6 (2012), 550–559, 10.1038/pr.2012.123.
117. [117] Ren, L.P., Chan, S.M., Zeng, X.Y., et al. Differing endoplasmic reticulum stress response to excess lipogenesis versus lipid oversupply in relation to hepatic steatosis and insulin resistance. PLoS One, 7(2), 2012, e30816, 10.1371/journal.pone.0030816.
118. [118] Chan, S.M., Sun, R.Q., Zeng, X.Y., et al. Activation of PPARalpha ameliorates hepatic insulin resistance and steatosis in high fructose-fed mice despite increased endoplasmic reticulum stress. Diabetes 62:6 (2013), 2095–2105, 10.2337/db12-1397.
119. [119] Zhang, C., Chen, X., Zhu, R.M., et al. Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice. Toxicol Lett 212:3 (2012), 229–240, 10.1016/j.toxlet.2012.06.002.
120. [120] Wali, J.A., Rondas, D., McKenzie, M.D., et al. The proapoptotic BH3-only proteins bim and puma are downstream of endoplasmic reticulum and mitochondrial oxidative stress in pancreatic islets in response to glucotoxicity. Cell Death Dis, 5, 2014, e1124, 10.1038/cddis.2014.88.
121. [121] Zhong, Y., Wang, J.J., Zhang, S.X., Intermittent but not constant high glucose induces ER stress and inflammation in human retinal pericytes. Adv Exp Med Biol 723 (2012), 285–292, 10.1007/978-1-4614-0631-0_37.
122. [122] Jaiswal, N., Maurya, C.K., Arha, D., et al. Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress. Apoptosis 20:7 (2015), 930–947, 10.1007/s10495-015-1128-y.
123. [123] Bachar, E., Ariav, Y., Ketzinel-Gilad, M., Cerasi, E., Kaiser, N., Leibowitz, G., Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic beta-cells via activation of mTORC1. PLoS One, 4(3), 2009, e4954, 10.1371/journal.pone.0004954.