Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

References

• Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908–922. doi:10.1038/s41591-018-0104-9
   PubMed Web of Science ®Google Scholar
• Wong VW, Wong GL, Choi PC, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010;59(7):969–974. doi:10.1136/gut.2009.205088
   PubMed Web of Science ®Google Scholar
• Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005;42(1):132–138. doi:10.1016/j.jhep.2004.09.012
   PubMed Web of Science ®Google Scholar
• Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Am J Gastroenterol. 2003;98(9):2042–2047. doi:10.1111/j.1572-0241.2003.07659.x
   PubMed Web of Science ®Google Scholar
• Evans CD, Oien KA, MacSween RN, et al. Non-alcoholic steatohepatitis: a common cause of progressive chronic liver injury?. J Clin Pathol. 2002;55(9):689–692. doi:10.1136/jcp.55.9.689
   Web of Science ®Google Scholar
• Fassio E, Alvarez E, Domínguez N, et al. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004;40(4):820–826. doi:10.1002/hep.20410
   PubMed Web of Science ®Google Scholar
• Hui AY, Wong VW, Chan HL, et al. Histological progression of non-alcoholic fatty liver disease in Chinese patients. Aliment Pharmacol Ther. 2005;21(4):407–413. doi:10.1111/j.1365-2036.2005.02334.x
   Web of Science ®Google Scholar
• Argo CK, Northup PG, Al-Osaimi AM, et al. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol. 2009;51(2):371–379. doi:10.1016/j.jhep.2009.03.019
   PubMed Web of Science ®Google Scholar
• Matteoni CA, Younossi ZM, Gramlich T, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413–1419. doi:10.1016/s0016-5085(99)70506-8
   PubMed Web of Science ®Google Scholar
• Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44(4):865–873. doi:10.1002/hep.21327
   PubMed Web of Science ®Google Scholar
• McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis. 2004;8(3):521–533. doi:10.1016/j.cld.2004.04.004
   PubMedGoogle Scholar
• Önnerhag K, Nilsson PM, Lindgren S. Increased risk of cirrhosis and hepatocellular cancer during long-term follow-up of patients with biopsy-proven NAFLD. Scand J Gastroenterol. 2014;49(9):1111–1118. doi:10.3109/00365521.2014.934911
   PubMed Web of Science ®Google Scholar
• Cholankeril G, Patel R, Khurana S, et al. Hepatocellular carcinoma in non-alcoholic steatohepatitis: current knowledge and implications for management. World J Hepatol. 2017;9(11):533–543. doi:10.4254/wjh.v9.i11.533
   PubMed Web of Science ®Google Scholar
• Ganne-Carrié N, Chastang C, Chapel F, et al. Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis. Hepatology. 1996;23(5):1112–1118. doi:10.1002/hep.510230527
   Web of Science ®Google Scholar
• Trinchet JC, Bourcier V, Chaffaut C, et al. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology. 2015;62(3):737–750. doi:10.1002/hep.27743
   PubMed Web of Science ®Google Scholar
• White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(12):1342–1359.e2. doi:10.1016/j.cgh.2012.10.001
   PubMed Web of Science ®Google Scholar
• Mantovani A, Scorletti E, Mosca A, et al. Complications, morbidity and mortality of nonalcoholic fatty liver disease. Metabolism. 2020;111S:154170. doi:10.1016/j.metabol.2020.154170
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. doi:10.1002/hep.28431
   PubMed Web of Science ®Google Scholar
• Zou B, Yeo YH, Nguyen VH, et al. Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999–2016. J Intern Med. 2020;288(1):139–151. doi:10.1111/joim.13069
   PubMed Web of Science ®Google Scholar
• Le MH, Yeo YH, Cheung R, et al. Ethnic influence on nonalcoholic fatty liver disease prevalence and lack of disease awareness in the United States, 2011–2016. J Intern Med. 2020;287(6):711–722. doi:10.1111/joim.13035
   PubMed Web of Science ®Google Scholar
• Li J, Zou B, Yeo YH, et al. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999–2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2019;4(5):389–398. doi:10.1016/S2468-1253(19)30039-1
   PubMed Web of Science ®Google Scholar
• Sivell C. nonalcoholic fatty liver disease: a silent epidemic. Gastroenterol Nurs. 2019;42(5):428–434. doi:10.1097/SGA.0000000000000443
   Web of Science ®Google Scholar
• Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65(8):1038–1048. doi:10.1016/j.metabol.2015.12.012
   PubMed Web of Science ®Google Scholar
• Alkhalidy H, Moore W, Wang A, et al. Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice. J Nutr Biochem. 2018;58:90–101. doi:10.1016/j.jnutbio.2018.04.014
   PubMed Web of Science ®Google Scholar
• Lordan R, Tsoupras A, Zabetakis I, et al. Forty years since the structural elucidation of platelet-activating factor (PAF): historical, current, and future research perspectives. Molecules. 2019;24(23):4414. doi:10.3390/molecules24234414
   PubMed Web of Science ®Google Scholar
• Oral A, Sahin T, Turker F, et al. Evaluation of plateletcrit and platelet distribution width in patients with non-alcoholic fatty liver disease: a retrospective chart review study. Med Sci Monit. 2019;25:9882–9886. doi:10.12659/MSM.920172
   Web of Science ®Google Scholar
• Ozhan H, Aydin M, Yazici M, et al. Mean platelet volume in patients with non-alcoholic fatty liver disease. Platelets. 2010;21(1):29–32. doi:10.3109/09537100903391023
   PubMed Web of Science ®Google Scholar
• Arslan N, Makay B. Mean platelet volume in obese adolescents with nonalcoholic fatty liver disease. J Pediatr Endocrinol Metab. 2010;23(8):807–813. doi:10.1515/jpem.2010.130
   PubMed Web of Science ®Google Scholar
• Malehmir M, Pfister D, Gallage S, et al. Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer. Nat Med. 2019;25(4):641–655. doi:10.1038/s41591-019-0379-5
   PubMed Web of Science ®Google Scholar
• Jiang ZG, Feldbrügge L, Tapper EB, et al. Aspirin use is associated with lower indices of liver fibrosis among adults in the United States. Aliment Pharmacol Ther. 2016;43(6):734–743. doi:10.1111/apt.13515
   PubMed Web of Science ®Google Scholar
• Armstrong MJ, Rowe IA. Editorial: would an aspirin a day keep NAFLD and its complications away?. Aliment Pharmacol Ther. 2015;41(1):145. doi:10.1111/apt.12998
   Web of Science ®Google Scholar
• Shen H, Shahzad G, Jawairia M, et al. Association between aspirin use and the prevalence of nonalcoholic fatty liver disease: a cross-sectional study from the Third National Health and Nutrition Examination Survey. Aliment Pharmacol Ther. 2014;40(9):1066–1073. doi:10.1111/apt.12944
   PubMed Web of Science ®Google Scholar
• Simon TG, Henson J, Osganian S, et al. Daily aspirin use associated with reduced risk for fibrosis progression in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2019;17(13):2776–2784.e4. doi:10.1016/j.cgh.2019.04.061
   PubMed Web of Science ®Google Scholar
• Wang W, Chen J, Mao J, et al. Genistein Ameliorates Non-alcoholic Fatty Liver Disease by Targeting the Thromboxane A2 Pathway. J Agric Food Chem. 2018;66(23):5853–5859. doi:10.1021/acs.jafc.8b01691
   Web of Science ®Google Scholar
• Ford RJ, Fullerton MD, Pinkosky SL, et al. Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochem J. 2015;468(1):125–132. doi:10.1042/BJ20150125
   PubMed Web of Science ®Google Scholar
• Fujita K, Nozaki Y, Wada K, et al. Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease. Gut. 2008;57(11):1583–1591. doi:10.1136/gut.2007.144550
   Web of Science ®Google Scholar
• Ibrahim M, Farghaly E, Gomaa W, et al. Nitro-aspirin is a potential therapy for non alcoholic fatty liver disease. Eur J Pharmacol. 2011;659(2–3):289–295. doi:10.1016/j.ejphar.2011.03.016
   Web of Science ®Google Scholar
• Kunz D, Gerard NP, Gerard C. The human leukocyte platelet-activating factor receptor. cDNA cloning, cell surface expression, and construction of a novel epitope-bearing analog. J Biol Chem. 1992;267(13):9101–9106.
   Web of Science ®Google Scholar
• Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev. 2000;80(4):1669–1699. doi:10.1152/physrev.2000.80.4.1669
   PubMed Web of Science ®Google Scholar
• Marrache AM, F G, Bernier SG, et al. Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor. J Immunol. 2002;169(11):6474–6481. doi:10.4049/jimmunol.169.11.6474
   PubMed Web of Science ®Google Scholar
• Greco NJ, Arnold JH, O’Dorisio TM, et al. Action of platelet-activating factor on type 1 diabetic human platelets. J Lab Clin Med. 1985;105(4):410–416.
   Web of Science ®Google Scholar
• O’Donnell MC, Henson PM, Fiedel BA. Activation of human platelets by platelet activating factor (PAF) derived from sensitized rabbit basophils. Immunology. 1978;35(6):953–958.
   Web of Science ®Google Scholar
• Murphy CT, Elmore M, Kellie S, et al. Comparison of the role of protein kinase C in platelet functional responses induced by three different mechanisms, PAF, ionomycin and arachidonic acid. Biochim Biophys Acta. 1991;1133:46–54.
   Web of Science ®Google Scholar
• Pédrono F, Cheminade C, Legrand AB. Natural 1-O-alkylglycerols reduce platelet-activating factor-induced release of [3H]-serotonin in rabbit platelets. Prostaglandins Leukot Essent Fatty Acids. 2004;71(1):19–23. doi:10.1016/j.plefa.2003.12.003
   Web of Science ®Google Scholar
• Brooks AC, Menzies-Gow NJ, Wheeler-Jones CP, et al. Regulation of platelet activating factor-induced equine platelet activation by intracellular kinases. J Vet Pharmacol Ther. 2009;32(2):189–196. doi:10.1111/j.1365-2885.2008.01020.x
   Web of Science ®Google Scholar
• Bailey SR, Andrews MJ, Elliott J, et al. Differential activation of platelets from normal and allergic ponies by PAF and ADP. Inflamm Res. 2000;49(5):224–230. doi:10.1007/s000110050583
   Web of Science ®Google Scholar
• El-Merahbi R, Löffler M, Mayer A, et al. The roles of peripheral serotonin in metabolic homeostasis. FEBS Lett. 2015;589(15):1728–1734. doi:10.1016/j.febslet.2015.05.054
   PubMed Web of Science ®Google Scholar
• Bajrangee A, Ryan N, Vangjeli C, et al. Impact of genetic variation in the 5-HT transporter and receptor on platelet function in patients with stable CAD taking aspirin. Thromb Res. 2016;146:51–55. doi:10.1016/j.thromres.2016.08.019
   Web of Science ®Google Scholar
• Qing P, Hao J, Xiquan K, et al.. The role of serotonin in concanavalin A-induced liver injury in mice. Oxid Med Cell Longev. 2020:7504521. doi:10.1155/2020/7504521
   Web of Science ®Google Scholar
• Lesurtel M, Soll C, Humar B, et al. Serotonin: a double-edged sword for the liver?. Surgeon. 2012;10(2):107–113. doi:10.1016/j.surge.2011.11.002
   Web of Science ®Google Scholar
• Choi WG, Choi W, Oh TJ, et al. Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance. J Clin Invest. 2021;131(23):e145331. doi:10.1172/JCI145331
   Web of Science ®Google Scholar
• Fu J, Li C, Zhang G, et al. Crucial roles of 5-HT and 5-HT2 receptor in diabetes-related lipid accumulation and pro-inflammatory cytokine generation in hepatocytes. Cell Physiol Biochem. 2018;48(6):2409–2428. doi:10.1159/000492656
   Google Scholar
• Fu J, Ma S, Li X, et al. Long-term Stress with hyperglucocorticoidemia-induced hepatic steatosis with VLDL overproduction is dependent on both 5-HT2 receptor and 5-HT synthesis in liver. Int J Biol Sci. 2016;12(2):219–234. doi:10.7150/ijbs.13062
   Web of Science ®Google Scholar
• Lulu W, Xiangcheng F, Jichun H, et al. Gut-derived serotonin contributes to the progression of non-alcoholic steatohepatitis the liver HTR2A/PPARγ2 pathway. Front Pharmacol. 2020;11:553. doi:10.3389/fphar.2020.00553
   Web of Science ®Google Scholar
• Osawa Y, Kanamori H, Seki E, et al. L-tryptophan-mediated enhancement of susceptibility to nonalcoholic fatty liver disease is dependent on the mammalian target of rapamycin. J Biol Chem. 2011;286(40):34800–34808. doi:10.1074/jbc.M111.235473
   PubMed Web of Science ®Google Scholar
• Namkung J, Shong KE, Kim H, et al. Inhibition of serotonin synthesis induces negative hepatic lipid balance. Diabetes Metab J. 2018;42(3):233–243. doi:10.4093/dmj.2017.0084
   Web of Science ®Google Scholar
• Choi W, Namkung J, Hwang I, et al. Serotonin signals through a gut-liver axis to regulate hepatic steatosis. Nat Commun. 2018;9(1):4824. doi:10.1038/s41467-018-07287-7
   PubMed Web of Science ®Google Scholar
• Crane JD, Palanivel R, Mottillo EP, et al. Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat Med. 2015;21(2):166–172. doi:10.1038/nm.3766
   PubMed Web of Science ®Google Scholar
• Nocito A, Dahm F, Jochum W, et al. Serotonin mediates oxidative stress and mitochondrial toxicity in a murine model of nonalcoholic steatohepatitis. Gastroenterology. 2007;133(2):608–618. doi:10.1053/j.gastro.2007.05.019
   PubMed Web of Science ®Google Scholar
• Tintinger GR, Theron AJ, Steel HC, et al. Protein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase C. J Inflamm. 2009;6:29. doi:10.1186/1476-9255-6-29
   Google Scholar
• Sakon M, Kambayashi J. The regulatory mechanism of free Ca2+ concentration in activated platelets. Nihon Rinsho. 1992;50:249–253.
   Google Scholar
• Yu P, Hatakeyama T, Aramoto H, et al. Mitogen-activated protein kinases regulate platelet-activating factor-induced hyperpermeability. Microcirculation. 2005;12(8):637–643. doi:10.1080/10739680500301706
   Web of Science ®Google Scholar
• Ng DS, Wong K. Platelet-activating factor (PAF) stimulates phosphatidylinositol hydrolysis in human peripheral blood mononuclear leukocytes. Res Commun Chem Pathol Pharmacol. 1989;66(2):219–231.
   Google Scholar
• Abebe W, Ali N, Agrawal DK. Platelet-activating factor-induced inositol 1,4,5-trisphosphate generation in undifferentiated and differentiated U937 cells: role of tyrosine kinase. Int J Immunopharmacol. 1996;18(3):173–181. doi:10.1016/0192-0561(96)00004-5
   Web of Science ®Google Scholar
• Lin AY, Rui YC. Platelet-activating factor induced calcium mobilization and phosphoinositide metabolism in cultured bovine cerebral microvascular endothelial cells. Biochim Biophys Acta. 1994;1224(2):323–328. doi:10.1016/0167-4889(94)90206-2
   Web of Science ®Google Scholar
• Koike H, Imanishi N, Natsume Y, et al. Effects of platelet activating factor receptor antagonists on intracellular platelet activating factor function in neutrophils. Eur J Pharmacol. 1994;269(3):299–309. doi:10.1016/0922-4106(94)90037-x
   Web of Science ®Google Scholar
• Okayasu T, Hasegawa K, Ishibashi T. Platelet-activating factor stimulates metabolism of phosphoinositides via phospholipase A2 in primary cultured rat hepatocytes. J Lipid Res. 1987;28(7):760–767.
   Web of Science ®Google Scholar
• Chu WF, Sun HL, Dong DL, et al. Increasing Intracellular calcium of Guinea pig ventricular myocytes induced by platelet activating factor through IP3 pathway. Basic Clin Pharmacol Toxicol. 2006;98(1):104–109. doi:10.1111/j.1742-7843.2006.pto_313.x
   Web of Science ®Google Scholar
• Lautenschläger I, Wong YL, Sarau J, et al. Signalling mechanisms in PAF-induced intestinal failure. Sci Rep. 2017;7(1):13382. doi:10.1038/s41598-017-13850-x
   Web of Science ®Google Scholar
• Pedreño J, Hurt-Camejo E, Wiklund O, et al. Low-density lipoprotein (LDL) binds to a G-protein coupled receptor in human platelets. Evidence that the proaggregatory effect induced by LDL is modulated by down-regulation of binding sites and desensitization of its mediated signaling. Atherosclerosis. 2001;155(1):99–112. doi:10.1016/s0021-9150(00)00545-1
   Web of Science ®Google Scholar
• Raffaello A, Mammucari C, Gherardi G, et al. Calcium at the center of cell signaling: interplay between endoplasmic reticulum, mitochondria, and lysosomes. Trends Biochem Sci. 2016;41(12):1035–1049. doi:10.1016/j.tibs.2016.09.001
   PubMed Web of Science ®Google Scholar
• Groenendyk J, Agellon LB, Michalak M. Calcium signaling and endoplasmic reticulum stress. Int Rev Cell Mol Biol. 2021;363:1–20. doi:10.1016/bs.ircmb.2021.03.003
   PubMed Web of Science ®Google Scholar
• Szabadkai G, Bianchi K, Várnai P, et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol. 2006;175(6):901–911. doi:10.1083/jcb.200608073
   PubMed Web of Science ®Google Scholar
• Marchi S, Bittremieux M, Missiroli S, et al. Endoplasmic reticulum-mitochondria communication through Ca2+ signaling: the importance of mitochondria-associated membranes (MAMs). Adv Exp Med Biol. 2017;997:49–67. doi:10.1007/978-981-10-4567-7_4
   Web of Science ®Google Scholar
• Hirata K, Pusl T, O’Neill AF, et al. The type II inositol 1,4,5-trisphosphate receptor can trigger Ca2+ waves in rat hepatocytes. Gastroenterology. 2002;122(4):1088–1100. doi:10.1053/gast.2002.32363
   PubMed Web of Science ®Google Scholar
• Khamphaya T, Chukijrungroat N, Saengsirisuwan V, et al. Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5-trisphosphate receptor. Hepatology. 2018;67(2):560–574. doi:10.1002/hep.29588
   PubMed Web of Science ®Google Scholar
• Arruda AP, Pers BM, Parlakgül G, et al. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity. Nat Med. 2014;20(12):1427–1435. doi:10.1038/nm.3735
   PubMed Web of Science ®Google Scholar
• Feriod CN, Oliveira AG, Guerra MT, et al. Hepatic Inositol 1,4,5 Trisphosphate Receptor Type 1 Mediates Fatty Liver. Hepatol Commun. 2017;1(1):23–35. doi:10.1002/hep4.1012
   Web of Science ®Google Scholar
• Alzayady KJ, Wang L, Chandrasekhar R, et al. Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca2+ release. Sci Signal. 2016;9(422):ra35. doi:10.1126/scisignal.aad6281
   Web of Science ®Google Scholar
• Barritt GJ, Litjens TL, Castro J, et al. Store-operated Ca2+ channels and microdomains of Ca2+ in liver cells. Clin Exp Pharmacol Physiol. 2009;36(1):77–83. doi:10.1111/j.1440-1681.2008.05095.x
   Web of Science ®Google Scholar
• Ong HL, Ambudkar IS. STIM-TRP pathways and microdomain organization: contribution of TRPC1 in store-operated Ca2+ entry: impact on Ca2+ signaling and cell function. Adv Exp Med Biol. 2017;993:159–188. doi:10.1007/978-3-319-57732-6_9
   Web of Science ®Google Scholar
• Thillaiappan NB, Chakraborty P, Hasan G, et al. IP3 receptors and Ca2+ entry. Biochim Biophys Acta Mol Cell Res. 2019;1866(7):1092–1100. doi:10.1016/j.bbamcr.2018.11.007
   Web of Science ®Google Scholar
• Zhang L, Zhang Y, Jiang Y, et al. Upregulated SOCC and IP3R calcium channels and subsequent elevated cytoplasmic calcium signaling promote nonalcoholic fatty liver disease by inhibiting autophagy. Mol Cell Biochem. 2021;476(8):3163–3175. doi:10.1007/s11010-021-04150-0
   Web of Science ®Google Scholar
• Hammadi M, Oulidi A, Gackière F, et al. Modulation of ER stress and apoptosis by endoplasmic reticulum calcium leak via translocon during unfolded protein response: involvement of GRP78. FASEB J. 2013;27(4):1600–1609. doi:10.1096/fj.12-218875
   Web of Science ®Google Scholar
• Lai S, Li Y, Kuang Y, et al. PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity. Biosci Rep. 2017;37(6):BSR20170869. doi:10.1042/BSR20170869
   Web of Science ®Google Scholar
• Zhang J, Li Y, Jiang S, et al. Enhanced endoplasmic reticulum SERCA activity by overexpression of hepatic stimulator substance gene prevents hepatic cells from ER stress-induced apoptosis. Am J Physiol Cell Physiol. 2014;306(3):C279–C290. doi:10.1152/ajpcell.00117.2013
   Web of Science ®Google Scholar
• Zeeshan HM, Lee GH, Kim HR, et al. Endoplasmic reticulum stress and associated ROS. Int J Mol Sci. 2016;17(3):327. doi:10.3390/ijms17030327
   PubMed Web of Science ®Google Scholar
• Lebeaupin C, Vallée D, Hazari Y, et al. Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol. 2018;69(4):927–947. doi:10.1016/j.jhep.2018.06.008
   PubMed Web of Science ®Google Scholar
• Vallée D, Blanc M, Lebeaupin C, et al. La réponse au stress du réticulum endoplasmique dans la physiopathologie des maladies chroniques du foie [Endoplasmic reticulum stress response and pathogenesis of non-alcoholic steatohepatitis]. Med Sci. 2020;36(2):119–129. doi:10.1051/medsci/2020008
   Web of Science ®Google Scholar
• Zhang J, Zhang K, Li Z, et al. ER stress-induced inflammasome activation contributes to hepatic inflammation and steatosis. J Clin Cell Immunol. 2016;7(5):457. doi:10.4172/2155-9899.1000457
   Google Scholar
• Xu Y, Yang C, Zhang S, et al. Ginsenoside Rg1 protects against non-alcoholic fatty liver disease by ameliorating lipid peroxidation, endoplasmic reticulum stress, and inflammasome activation. Biol Pharm Bull. 2018;41(11):1638–1644. doi:10.1248/bpb.b18-00132
   PubMed Web of Science ®Google Scholar
• Ye L, Zhao D, Xu Y, et al. LncRNA-Gm9795 promotes inflammation in non-alcoholic steatohepatitis via NF-[Formula: see text]B/JNK pathway by endoplasmic reticulum stress. J Transl Med. 2021;19(1):101. doi:10.1186/s12967-021-02769-7
   Web of Science ®Google Scholar
• Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306(5695):457–461. doi:10.1126/science.1103160
   PubMed Web of Science ®Google Scholar
• Murakami M, Kudo I. Phospholipase A2. J Biochem. 2002;131(3):285–292. doi:10.1093/oxfordjournals.jbchem.a003101
   PubMed Web of Science ®Google Scholar
• Catalán RE, Martínez AM, Aragonés MD, et al. PAF and thrombin actions in platelets are selectively affected by a new 1,4-dihydropyridine derivative. J Biochem. 1993;113(4):450–455. doi:10.1093/oxfordjournals.jbchem.a124065
   Web of Science ®Google Scholar
• Oestvang J, Anthonsen MW, Johansen B. LysoPC and PAF trigger arachidonic acid release by divergent signaling mechanisms in monocytes. J Lipids. 2011;2011:532145. doi:10.1155/2011/532145
   PubMedGoogle Scholar
• Hurst JS, Bazan HE. Platelet-activating factor preferentially stimulates the phospholipase A2/cyclooxygenase cascade in the rabbit cornea. Curr Eye Res. 1995;14(9):769–775. doi:10.3109/02713689508995798
   PubMed Web of Science ®Google Scholar
• Svetlov SI, Howard KM, Miwa M, et al. Interaction of platelet-activating factor with rat hepatocytes: uptake, translocation, metabolism, and effects on PAF-acetylhydrolase secretion and protein tyrosine phosphorylation. Arch Biochem Biophys. 1996;327(1):113–122. doi:10.1006/abbi.1996.0099
   Web of Science ®Google Scholar
• Burns JL, Nakamura MT, Ma DWL. Differentiating the biological effects of linoleic acid from arachidonic acid in health and disease. Prostaglandins Leukot Essent Fatty Acids. 2018;135:1–4. doi:10.1016/j.plefa.2018.05.004
   PubMed Web of Science ®Google Scholar
• Sonnweber T, Pizzini A, Nairz M, et al. Arachidonic acid metabolites in cardiovascular and metabolic diseases. Int J Mol Sci. 2018;19(11):3285. doi:10.3390/ijms19113285
   PubMed Web of Science ®Google Scholar
• Innes JK, Calder PC. Omega-6 fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids. 2018;132:41–48. doi:10.1016/j.plefa.2018.03.004
   PubMed Web of Science ®Google Scholar
• Di Nunzio M, Valli V, Bordoni A. PUFA and oxidative stress. Differential modulation of the cell response by DHA. Int J Food Sci Nutr. 2016;67(7):834–843. doi:10.1080/09637486.2016.1201790
   PubMed Web of Science ®Google Scholar
• Samala N, Tersey SA, Chalasani N, et al. Molecular mechanisms of nonalcoholic fatty liver disease: potential role for 12-lipoxygenase. J Diabetes Complications. 2017;31(11):1630–1637. doi:10.1016/j.jdiacomp.2017.07.014
   PubMed Web of Science ®Google Scholar
• Garrido D, Chanteloup NK, Trotereau A, et al. Characterization of the phospholipid platelet-activating factor as a mediator of inflammation in chickens. Front Vet Sci. 2017;4:226. doi:10.3389/fvets.2017.00226
   PubMed Web of Science ®Google Scholar
• Dalmaso B, da Silva-Junior IA, Fragel-Madeira L, et al. Platelet activating factor in the eye: physiological roles, diseases and future perspectives. Prostaglandins Other Lipid Mediat. 2021;153:106522. doi:10.1016/j.prostaglandins.2020.106522
   Web of Science ®Google Scholar
• Evans JH, Spencer DM, Zweifach A, et al. Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes. J Biol Chem. 2001;276(32):30150–30160. doi:10.1074/jbc.M100943200
   Web of Science ®Google Scholar
• Six DA, Dennis EA. Essential Ca(2+)-independent role of the group IVA cytosolic phospholipase A(2) C2 domain for interfacial activity. J Biol Chem. 2003;278(26):23842–23850. doi:10.1074/jbc.M301386200
   Web of Science ®Google Scholar
• Singh MK, Jayarajan R, Varshney S, et al. Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1866(5):158905. doi:10.1016/j.bbalip.2021.158905
   Web of Science ®Google Scholar
• Musso G, Gambino R, Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obes Rev. 2010;11(6):430–445. doi:10.1111/j.1467-789X.2009.00657.x
   PubMed Web of Science ®Google Scholar
• Colak Y, Senates E, Ozturk O, et al. Association of serum lipoprotein-associated phospholipase A2 level with nonalcoholic fatty liver disease. Metab Syndr Relat Disord. 2012;10(2):103–109. doi:10.1089/met.2011.0111
   Web of Science ®Google Scholar
• Zelber-Sagi S, Azar S, Nemirovski A, et al. Serum levels of endocannabinoids are independently associated with nonalcoholic fatty liver disease. Obesity. 2017;25(1):94–101. doi:10.1002/oby.21687
   Web of Science ®Google Scholar
• Tutino V, De Nunzio V, Caruso MG, et al. Aerobic physical activity and a low glycemic diet reduce the AA/EPA ratio in red blood cell membranes of patients with NAFLD. Nutrients. 2018;10(9):1299. doi:10.3390/nu10091299
   Web of Science ®Google Scholar
• Ii H, Yokoyama N, Yoshida S, et al. Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice. PLoS One. 2009;4(12):e8089. doi:10.1371/journal.pone.0008089
   Web of Science ®Google Scholar
• Sztolsztener K, Chabowski A, Harasim-Symbor E, et al. Arachidonic acid as an early indicator of inflammation during non-alcoholic fatty liver disease development. Biomolecules. 2020;10(8):1133. doi:10.3390/biom10081133
   PubMed Web of Science ®Google Scholar
• Ma K, Chen Y, Liang X, et al. Inhibition of 5-lipoxygenase inhibitor zileuton in high-fat diet-induced nonalcoholic fatty liver disease progression model. Iran J Basic Med Sci. 2017;20(11):1207–1212. doi:10.22038/IJBMS.2017.9482
   Web of Science ®Google Scholar
• Ghazali R, Mehta KJ, Bligh SA, et al. High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells. World J Hepatol. 2020;12(3):84–98. doi:10.4254/wjh.v12.i3.84
   Web of Science ®Google Scholar
• Fiorio Pla A, Genova T, Pupo E, et al. Multiple roles of protein kinase a in arachidonic acid-mediated Ca2+ entry and tumor-derived human endothelial cell migration. Mol Cancer Res. 2010;8(11):1466–1476. doi:10.1158/1541-7786.MCR-10-0002
   Web of Science ®Google Scholar
• Thompson J, Mignen O, Shuttleworth TJ. The N-terminal domain of Orai3 determines selectivity for activation of the store-independent ARC channel by arachidonic acid. Channels. 2010;4(5):398–410. doi:10.4161/chan.4.5.13226
   PubMed Web of Science ®Google Scholar
• Tseng CL, Wei JW. Homologous desensitization of histamine-mediated signal transduction system in C6 glioma cells. Chin J Physiol. 2013;56(2):90–100. doi:10.4077/CJP.2013.BAB094
   Web of Science ®Google Scholar
• Martínez J, Moreno JJ. Role of Ca2+-independent phospholipase A2 on arachidonic acid release induced by reactive oxygen species. Arch Biochem Biophys. 2001;392(2):257–262. doi:10.1006/abbi.2001.2439
   PubMed Web of Science ®Google Scholar
• Nunemaker CS, Chen M, Pei H, et al. 12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet. Am J Physiol Endocrinol Metab. 2008;295(5):E1065–E1075. doi:10.1152/ajpendo.90371.2008
   Web of Science ®Google Scholar
• Lazic M, Inzaugarat ME, Povero D, et al. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis. PLoS One. 2014;9(9):e107658. doi:10.1371/journal.pone.0107658
   PubMed Web of Science ®Google Scholar
• Martínez-Clemente M, Ferré N, González-Périz A, et al. 5-lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor alpha-induced hepatocyte damage in hyperlipidemia-prone ApoE-null mice. Hepatology. 2010;51(3):817–827. doi:10.1002/hep.23463
   Web of Science ®Google Scholar
• Puri P, Wiest MM, Cheung O, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology. 2009;50(6):1827–1838. doi:10.1002/hep.23229
   PubMed Web of Science ®Google Scholar
• Hall Z, Bond NJ, Ashmore T, et al. Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease. Hepatology. 2017;65(4):1165–1180. doi:10.1002/hep.28953
   PubMed Web of Science ®Google Scholar
• Ma K, Nunemaker CS, Wu R, et al. 12-lipoxygenase products reduce insulin secretion and {beta}-cell viability in human islets. J Clin Endocrinol Metab. 2010;95(2):887–893. doi:10.1210/jc.2009-1102
   PubMed Web of Science ®Google Scholar
• Chakrabarti SK, Cole BK, Wen Y, Keller SR, Nadler JL. 12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. Obesity. 2009;17(9):1657–1663. doi:10.1038/oby.2009.192
   Web of Science ®Google Scholar
• Khan H, Gupta A, Singh TG, et al. Mechanistic insight on the role of leukotriene receptors in ischemic-reperfusion injury. Pharmacol Rep. 2021;73(5):1240–1254. doi:10.1007/s43440-021-00258-8
   PubMed Web of Science ®Google Scholar
• Lecomte M, Lecocq R, Dumont JE, et al. Covalent binding of arachidonic acid metabolites to human platelet proteins. Identification of prostaglandin H synthase as one of the modified substrates. J Biol Chem. 1990;265(9):5178–5187.
   Web of Science ®Google Scholar
• Otomo Y, Kanda Y, Yoshino Y, Otsuka T. Production of leukotrienes in rat Kupffer cells and hepatocytes by various inducers. Nihon Geka Gakkai Zasshi. 1993;94(3):234–241.
   Google Scholar
• Doskey CM, Fader KA, Nault R, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats. Toxicol Appl Pharmacol. 2020;398:115034. doi:10.1016/j.taap.2020.115034
   Web of Science ®Google Scholar
• Takasugi M, Muta E, Yamada K, et al. A new method to evaluate anti-allergic effect of food component by measuring leukotriene B4 from a mouse mast cell line. Cytotechnology. 2018;70(1):177–184. doi:10.1007/s10616-017-0129-9
   Web of Science ®Google Scholar
• Ito S, Ito Y, Katagiri H, et al. Leukotriene B4/leukotriene B4 receptor pathway is involved in hepatic microcirculatory dysfunction elicited by endotoxin. Shock. 2008;30(1):87–91. doi:10.1097/shk.0b013e31815d06a1
   Web of Science ®Google Scholar
• Alvarez ML, Lorenzetti F. Role of eicosanoids in liver repair, regeneration and cancer. Biochem Pharmacol. 2021;192:114732. doi:10.1016/j.bcp.2021.114732
   Web of Science ®Google Scholar
• Gong M, Duan H, Wu F, et al. Berberine alleviates insulin resistance and inflammation via inhibiting the LTB4-BLT1 axis. Front Pharmacol. 2021;12:722360. doi:10.3389/fphar.2021.722360
   Web of Science ®Google Scholar
• Gai Z, Visentin M, Gui T, et al. Effects of farnesoid X receptor activation on arachidonic acid metabolism, NF-kB signaling, and hepatic inflammation. Mol Pharmacol. 2018;94(2):802–811. doi:10.1124/mol.117.111047
   Web of Science ®Google Scholar
• López-Parra M, Titos E, Horrillo R, et al. Regulatory effects of arachidonate 5-lipoxygenase on hepatic microsomal TG transfer protein activity and VLDL-triglyceride and apoB secretion in obese mice. J Lipid Res. 2008;49(12):2513–2523. doi:10.1194/jlr.M800101-JLR200
   Web of Science ®Google Scholar
• Horrillo R, González-Périz A, Martínez-Clemente M, et al. 5-lipoxygenase activating protein signals adipose tissue inflammation and lipid dysfunction in experimental obesity. J Immunol. 2010;184(7):3978–3987. doi:10.4049/jimmunol.0901355
   Web of Science ®Google Scholar
• Bäck M, Sultan A, Ovchinnikova O, et al. 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation. Circ Res. 2007;100(7):946–949. doi:10.1161/01.RES.0000264498.60702.0d
   PubMed Web of Science ®Google Scholar
• Gilbert NC, Gerstmeier J, Schexnaydre EE, et al. Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products. Nat Chem Biol. 2020;16(7):783–790. doi:10.1038/s41589-020-0544-7
   PubMed Web of Science ®Google Scholar
• Chakrabarti SK, Wen Y, Dobrian AD, et al. Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats. Am J Physiol Endocrinol Metab. 2011;300(1):E175–E187. doi:10.1152/ajpendo.00203.2010
   Web of Science ®Google Scholar
• Spite M, Hellmann J, Tang Y, et al. Deficiency of the leukotriene B4 receptor, BLT-1, protects against systemic insulin resistance in diet-induced obesity. J Immunol. 2011;187(4):1942–1949. doi:10.4049/jimmunol.1100196
   Web of Science ®Google Scholar
• Abdallah MS, Eldeen AH, Tantawy SS, et al. The leukotriene receptor antagonist montelukast in the treatment of non-alcoholic steatohepatitis: a proof-of-concept, randomized, double-blind, placebo-controlled trial. Eur J Pharmacol. 2021;906:174295. doi:10.1016/j.ejphar.2021.174295
   Web of Science ®Google Scholar
• Beara I, Majkić T, Fioravanti S, et al. The effects of trifluoromethylated derivatives on prostaglandin E2 and thromboxane A2 production in human leukemic U937 macrophages. Med Chem. 2020;16(1):63–68. doi:10.2174/1573406415666190208150253
   Web of Science ®Google Scholar
• Son DJ, Cho MR, Jin YR, et al. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids. 2004;71(1):25–31. doi:10.1016/j.plefa.2003.12.004
   Web of Science ®Google Scholar
• Srivastava KC. Transformations of exogenous arachidonic acid in human platelets in the presence of oleic- and eicosapentaenoic acids. Prostaglandins Leukot Med. 1985;18(1):31–37. doi:10.1016/0262-1746(85)90047-2
   Google Scholar
• Levine L. Platelet-activating factor stimulates arachidonic acid metabolism in rat liver cells (C-9 cell line) by a receptor-mediated mechanism. Mol Pharmacol. 1988;34(6):793–799.
   Web of Science ®Google Scholar
• Levine L. Effects of the protein kinase inhibitors, staurosporine and K-252a, on PGI2 production by rat liver cells (the C-9 cell line). Prostaglandins. 1990;40(3):259–269. doi:10.1016/0090-6980(90)90014-m
   Web of Science ®Google Scholar
• López-Parra M, Clària J, Titos E, et al. The selective cyclooxygenase-2 inhibitor celecoxib modulates the formation of vasoconstrictor eicosanoids and activates PPARgamma. Influence of Albumin J Hepatol. 2005;42(1):75–81. doi:10.1016/j.jhep.2004.09.011
   Web of Science ®Google Scholar
• Becker K, Heinroth-Hoffmann I, Giessler C, et al. PAF effects on eicosanoid release in neonatal rat cardiomyocytes. Prostaglandins Leukot Essent Fatty Acids. 1995;53(3):197–200. doi:10.1016/0952-3278(95)90116-7
   Web of Science ®Google Scholar
• Lo HM, Huang TF, Lin CN, et al. 2’-Ethoxy-5’-methoxy-2-(5-methylthienyl)chalcone inhibits collagen-induced protein tyrosine phosphorylation and thromboxane formation during platelet aggregation and adhesion. Pharmacology. 2009;84(3):145–152. doi:10.1159/000235584
   Web of Science ®Google Scholar
• Wang W, Zhong X, Guo J. Role of 2‑series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non‑alcoholic fatty liver disease (Review). Int J Mol Med. 2021;47(6):114. doi:10.3892/ijmm.2021.4947
   PubMed Web of Science ®Google Scholar
• Jiang J, Tran L, Vasudevan H, et al. Endothelin-1 blockade prevents COX2 induction and TXA2 production in the fructose hypertensive rat. Can J Physiol Pharmacol. 2007;85(3–4):422–429. doi:10.1139/y06-088
   Web of Science ®Google Scholar
• Rucker D, Dhamoon AS. Physiology, thromboxane A2. StatPearls; 2021.
   Google Scholar
• Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294(5548):1871–1875. doi:10.1126/science.294.5548.1871
   PubMed Web of Science ®Google Scholar
• Tipoe GL, Ho CT, Liong EC, et al. Voluntary oral feeding of rats not requiring a very high fat diet is a clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD). Histol Histopathol. 2009;24(9):1161–1169. doi:10.14670/HH-24.1161
   Web of Science ®Google Scholar
• Hybiak J, Broniarek I, Kiryczyński G, et al. Aspirin and its pleiotropic application. Eur J Pharmacol. 2020;866:172762. doi:10.1016/j.ejphar.2019.172762
   PubMed Web of Science ®Google Scholar
• Pérez S, Aspichueta P, Ochoa B, et al. The 2-series prostaglandins suppress VLDL secretion in an inflammatory condition-dependent manner in primary rat hepatocytes. Biochim Biophys Acta. 2006;1761(2):160–171. doi:10.1016/j.bbalip.2006.02.003
   Web of Science ®Google Scholar
• Feingold KR, Doerrler W, Dinarello CA, et al. Stimulation of lipolysis in cultured fat cells by tumor necrosis factor, interleukin-1, and the interferons is blocked by inhibition of prostaglandin synthesis. Endocrinology. 1992;130(1):10–16. doi:10.1210/endo.130.1.1370149
   PubMed Web of Science ®Google Scholar
• Henkel J, Frede K, Schanze N, et al. Stimulation of fat accumulation in hepatocytes by PGE-dependent repression of hepatic lipolysis, β-oxidation and VLDL-synthesis. Lab Invest. 2012;92(11):1597–1606. doi:10.1038/labinvest.2012.128
   Web of Science ®Google Scholar
• Nassir F, Adewole OL, Brunt EM, et al. CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice. J Lipid Res. 2013;54(11):2988–2997. doi:10.1194/jlr.M037812
   Web of Science ®Google Scholar
• Henkel J, Coleman CD, Schraplau A, et al. Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model. Sci Rep. 2018;8(1):16127. doi:10.1038/s41598-018-34633-y
   PubMed Web of Science ®Google Scholar
• Loomba R, Quehenberger O, Armando A, et al. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. J Lipid Res. 2015;56(1):185–192. doi:10.1194/jlr.P055640
   Web of Science ®Google Scholar
• Kus E, Kaczara P, Czyzynska-Cichon I, et al. LSEC fenestrae are preserved despite pro-inflammatory phenotype of liver sinusoidal endothelial cells in mice on high fat diet. Front Physiol. 2019;10:6. doi:10.3389/fphys.2019.00006
   Web of Science ®Google Scholar
• Kumei S, Yuhki KI, Kojima F, et al. Prostaglandin I2 suppresses the development of diet-induced nonalcoholic steatohepatitis in mice. FASEB J. 2018;32(5):2354–2365. doi:10.1096/fj.201700590R
   Web of Science ®Google Scholar
• Chung MY, Mah E, Masterjohn C, et al. Green tea lowers hepatic COX-2 and prostaglandin E2 in rats with dietary fat-induced nonalcoholic steatohepatitis. J Med Food. 2015;18(6):648–655. doi:10.1089/jmf.2014.0048
   Web of Science ®Google Scholar
• Helmersson J, Vessby B, Larsson A, et al. Association of type 2 diabetes with cyclooxygenase-mediated inflammation and oxidative stress in an elderly population. Circulation. 2004;109(14):1729–1734. doi:10.1161/01.CIR.0000124718.99562.91
   PubMed Web of Science ®Google Scholar
• Kimple ME, Keller MP, Rabaglia MR, et al. Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion. Diabetes. 2013;62(6):1904–1912. doi:10.2337/db12-0769
   PubMed Web of Science ®Google Scholar
• Batchu SN, Majumder S, Bowskill BB, et al. Prostaglandin I2 receptor agonism preserves β-cell function and attenuates albuminuria through nephrin-dependent mechanisms. Diabetes. 2016;65(5):1398–1409. doi:10.2337/db15-0783
   Web of Science ®Google Scholar
• Arablou T, Aryaeian N, Valizadeh M, et al. The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus. Int J Food Sci Nutr. 2014;65(4):515–520. doi:10.3109/09637486.2014.880671
   PubMed Web of Science ®Google Scholar
• Zhu CF, Li GZ, Peng HB, et al. Treatment with marine collagen peptides modulates glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus. Appl Physiol Nutr Metab. 2010;35(6):797–804. doi:10.1139/H10-075
   PubMed Web of Science ®Google Scholar
• Francés DE, Motiño O, Agrá N, et al. Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity, and insulin resistance. Diabetes. 2015;64(5):1522–1531. doi:10.2337/db14-0979
   Web of Science ®Google Scholar
• Hsieh PS, Jin JS, Chiang CF, et al. COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. Obesity. 2009;17(6):1150–1157. doi:10.1038/oby.2008.674
   PubMed Web of Science ®Google Scholar
• Henkel J, Neuschäfer-Rube F, Pathe-neuschäfer-rube A, et al. Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes. Hepatology. 2009;50(3):781–790. doi:10.1002/hep.23064
   Web of Science ®Google Scholar
• Henkel J, Gärtner D, Dorn C, et al. Oncostatin M produced in Kupffer cells in response to PGE2: possible contributor to hepatic insulin resistance and steatosis. Lab Invest. 2011;91(7):1107–1117. doi:10.1038/labinvest.2011.47
   Web of Science ®Google Scholar
• Wang Y, Yan S, Xiao B, et al. Prostaglandin F2α facilitates hepatic glucose production through camkiiγ/p38/FOXO1 signaling pathway in fasting and obesity. Diabetes. 2018;67(9):1748–1760. doi:10.2337/db17-1521
   Web of Science ®Google Scholar
• Sato N, Kaneko M, Tamura M, et al. The prostacyclin analog beraprost sodium ameliorates characteristics of metabolic syndrome in obese Zucker (fatty) rats. Diabetes. 2010;59(4):1092–1100. doi:10.2337/db09-1432
   Web of Science ®Google Scholar
• Ryu R, Kim HJ, Moon B, et al. Ethanol extract of persimmon tree leaves improves blood circulation and lipid metabolism in rats fed a high-fat diet. J Med Food. 2015;18(7):715–723. doi:10.1089/jmf.2014.3307
   Web of Science ®Google Scholar
• Francque S, Laleman W, Verbeke L, et al. Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture. Lab Invest. 2012;92(10):1428–1439. doi:10.1038/labinvest.2012.103
   PubMed Web of Science ®Google Scholar
• Nieuwenhuys CM, Feijge MA, Offermans RF, et al. Modulation of rat platelet activation by vessel wall-derived prostaglandin and platelet-derived thromboxane: effects of dietary fish oil on thromboxane-prostaglandin balance. Atherosclerosis. 2001;154(2):355–366. doi:10.1016/s0021-9150(00)00503-7
   Web of Science ®Google Scholar
• Murphy CT, Elmore M, Kellie S, et al. The relationship between cytosolic Ca2+, sn-1,2-diacylglycerol and inositol 1,4,5-trisphosphate elevation in platelet-activating-factor-stimulated rabbit platelets. Influence of protein kinase C on production of signal molecules. Biochem J. 1991;278(1):255–261. doi:10.1042/bj2780255
   Web of Science ®Google Scholar
• Catalán RE, Martínez AM, Aragonés MD, et al. PAF-induced activation of polyphosphoinositide-hydrolyzing phospholipase C in cerebral cortex. Biochem Biophys Res Commun. 1992;183(1):300–305. doi:10.1016/0006-291x(92)91643-5
   Web of Science ®Google Scholar
• Kester M, Thomas CP, Wang J, et al. Platelet-activating factor stimulates multiple signaling pathways in cultured rat mesangial cells. J Cell Physiol. 1992;153(2):244–255. doi:10.1002/jcp.1041530204
   Web of Science ®Google Scholar
• Uhing RJ, Prpic V, Hollenbach PW, et al. Involvement of protein kinase C in platelet-activating factor-stimulated diacylglycerol accumulation in murine peritoneal macrophages. J Biol Chem. 1989;264(16):9224–9230.
   Web of Science ®Google Scholar
• Miguel BG, Calcerrada MC, Martín L, et al. Increase of phosphoinositide hydrolysis and diacylglycerol production by PAF in isolated rat liver nuclei. Prostaglandins Other Lipid Mediat. 2001;65(4):159–166. doi:10.1016/s0090-6980(01)00124-1
   PubMed Web of Science ®Google Scholar
• Kojta I, Zabielski P, Roszczyc-Owsiejczuk K, et al. GPAT gene silencing in muscle reduces diacylglycerols content and improves insulin action in diet-induced insulin resistance. Int J Mol Sci. 2020;21(19):7369. doi:10.3390/ijms21197369
   Web of Science ®Google Scholar
• Preuss C, Jelenik T, Bódis K, et al. A new targeted lipidomics approach reveals lipid droplets in liver, muscle and heart as a repository for diacylglycerol and ceramide species in non-alcoholic fatty liver. Cells. 2019;8(3):277. doi:10.3390/cells8030277
   Web of Science ®Google Scholar
• Engin AB. What Is Lipotoxicity?. Adv Exp Med Biol. 2017;960:197–220. doi:10.1007/978-3-319-48382-5_8
   PubMed Web of Science ®Google Scholar
• Gorden DL, Ivanova PT, Myers DS, et al. Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model. PLoS One. 2011;6(8):e22775. doi:10.1371/journal.pone.0022775
   Web of Science ®Google Scholar
• Sanyal AJ, Pacana T. A lipidomic readout of disease progression in A diet-induced mouse model of nonalcoholic fatty liver disease. Trans Am Clin Climatol Assoc. 2015;126:271–288.
   PubMedGoogle Scholar
• Erion DM, Shulman GI. Diacylglycerol-mediated insulin resistance. Nat Med. 2010;16(4):400–402. doi:10.1038/nm0410-400
   PubMed Web of Science ®Google Scholar
• Gilijamse PW, Versteeg RI, Ackermans MT, et al. Hepatic diacylglycerol-associated protein kinase Cε translocation links hepatic steatosis to hepatic insulin resistance in humans. Cell Rep. 2017;19(10):1997–2004. doi:10.1016/j.celrep.2017.05.035
   Web of Science ®Google Scholar
• Yazıcı D, Sezer H. Insulin resistance, obesity and lipotoxicity. Adv Exp Med Biol. 2017;960:277–304. doi:10.1007/978-3-319-48382-5_12
   PubMed Web of Science ®Google Scholar
• Magkos F, Su X, Bradley D, et al. Intrahepatic diacylglycerol content is associated with hepatic insulin resistance in obese subjects. Gastroenterology. 2012;142(7):1444–6.e2. doi:10.1053/j.gastro.2012.03.003
   PubMed Web of Science ®Google Scholar
• Toulis KA, Nirantharakumar K, Pourzitaki C, et al. Glucokinase activators for type 2 diabetes: challenges and future developments. Drugs. 2020;80(5):467–475. doi:10.1007/s40265-020-01278-z
   PubMed Web of Science ®Google Scholar
• Sternisha SM, Miller BG. Molecular and cellular regulation of human glucokinase. Arch Biochem Biophys. 2019;663:199–213. doi:10.1016/j.abb.2019.01.011
   PubMed Web of Science ®Google Scholar
• Blackmore PF, Strickland WG, Bocckino SB, et al. Mechanism of hepatic glycogen synthase inactivation induced by Ca2+-mobilizing hormones. Studies using phospholipase C and phorbol myristate acetate. Biochem J. 1986;237(1):235–242. doi:10.1042/bj2370235
   Web of Science ®Google Scholar
• Hage hassan R, Bourron O, Hajduch E. Defect of insulin signal in peripheral tissues: important role of ceramide. World J Diabetes. 2014;5(3):244–257. doi:10.4239/wjd.v5.i3.244
   PubMedGoogle Scholar
• Titchenell PM, Lazar MA, Birnbaum MJ. Unraveling the regulation of hepatic metabolism by insulin. Trends Endocrinol Metab. 2017;28(7):497–505. doi:10.1016/j.tem.2017.03.003
   PubMed Web of Science ®Google Scholar
• Lewis GF, Carpentier AC, Pereira S, et al. Direct and indirect control of hepatic glucose production by insulin. Cell Metab. 2021;33(4):709–720. doi:10.1016/j.cmet.2021.03.007
   Web of Science ®Google Scholar
• Lyu K, Zhang Y, Zhang D, et al. A membrane-bound diacylglycerol species induces PKCϵ-mediated hepatic insulin resistance. Cell Metab. 2020;32(4):654–664.e5. doi:10.1016/j.cmet.2020.08.001
   Web of Science ®Google Scholar
• Aroor AR, Habibi J, Ford DA, et al. Dipeptidyl peptidase-4 inhibition ameliorates Western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function. Diabetes. 2015;64(6):1988–2001. doi:10.2337/db14-0804
   Web of Science ®Google Scholar
• Li X, Zhang D, Vatner DF, et al. Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. Proc Natl Acad Sci U S A. 2020;117(51):32584–32593. doi:10.1073/pnas.1922169117
   Web of Science ®Google Scholar
• Birkenfeld AL, Shulman GI. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology. 2014;59(2):713–723. doi:10.1002/hep.26672
   PubMed Web of Science ®Google Scholar
• Kumashiro N, Erion DM, Zhang D, et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2011;108(39):16381–16385. doi:10.1073/pnas.1113359108
   PubMed Web of Science ®Google Scholar
• Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294–S301. doi:10.1097/00003246-200205001-00020
   Web of Science ®Google Scholar
• Zaid Y, Senhaji N, Darif Y, et al. Distinctive roles of PKC delta isozyme in platelet function. Curr Res Transl Med. 2016;64(3):135–139. doi:10.1016/j.retram.2016.05.001
   Web of Science ®Google Scholar
• Pelech SL, Charest DL, Howard SL, et al. Protein kinase C activation by platelet-activating factor is independent of enzyme translocation. Biochim Biophys Acta. 1990;1051(1):100–107. doi:10.1016/0167-4889(90)90179-h
   Web of Science ®Google Scholar
• Gay JC, Stitt ES. Platelet-activating factor induces protein kinase activity in the particulate fraction of human neutrophils. Blood. 1988;71(1):159–165.
   Web of Science ®Google Scholar
• Hu H, Zhang W, Li N. Glycoprotein IIb/IIIa inhibition attenuates platelet-activating factor-induced platelet activation by reducing protein kinase C activity. J Thromb Haemost. 2003;1(8):1805–1812. doi:10.1046/j.1538-7836.2003.00324.x
   Web of Science ®Google Scholar
• Guo X, Zheng M, Pan R, et al. Hydroxysafflor yellow A (HSYA) targets the platelet-activating factor (PAF) receptor and inhibits human bronchial smooth muscle activation induced by PAF. Food Funct. 2019;10(8):4661–4673. doi:10.1039/c9fo00896a
   Web of Science ®Google Scholar
• Baudel MAS M-A, Shi J, Large WA, et al. Obligatory role for PKCδ in PIP2 -mediated activation of store-operated TRPC1 channels in vascular smooth muscle cells. J Physiol. 2020;598(18):3911–3925. doi:10.1113/JP279947
   Web of Science ®Google Scholar
• Sharma A, Maurya CK, Arha D, et al. Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes. Biochim Biophys Acta Mol Basis Dis. 2019;1865(1):136–146. doi:10.1016/j.bbadis.2018.10.036
   Web of Science ®Google Scholar
• Balciunaite E, Jones S, Toker A, et al. PDGF initiates two distinct phases of protein kinase C activity that make unequal contributions to the G0 to S transition. Curr Biol. 2000;10(5):261–267. doi:10.1016/s0960-9822(00)00358-4
   Web of Science ®Google Scholar
• Li M, Vienberg SG, Bezy O, et al. Role of PKCδ in insulin sensitivity and skeletal muscle metabolism. Diabetes. 2015;64(12):4023–4032. doi:10.2337/db14-1891
   Web of Science ®Google Scholar
• Morgan S, Yamanouchi D, Harberg C, et al. Elevated protein kinase C-δ contributes to aneurysm pathogenesis through stimulation of apoptosis and inflammatory signaling. Arterioscler Thromb Vasc Biol. 2012;32(10):2493–2502. doi:10.1161/ATVBAHA.112.255661
   PubMed Web of Science ®Google Scholar
• Lyu K, Zhang D, Song J, et al. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol/PKCε/insulin receptor Thr1160 phosphorylation. JCI Insight. 2021;6(4):e139946. doi:10.1172/jci.insight.139946
   Web of Science ®Google Scholar
• Malavez Y, Voss OH, Gonzalez-Mejia ME, et al. Distinct contribution of protein kinase Cδ and protein kinase Cε in the lifespan and immune response of human blood monocyte subpopulations. Immunology. 2015;144(4):611–620. doi:10.1111/imm.12412
   Web of Science ®Google Scholar
• Greene MW, Burrington CM, Luo Y, et al. PKCδ is activated in the liver of obese Zucker rats and mediates diet-induced whole body insulin resistance and hepatocyte cellular insulin resistance. J Nutr Biochem. 2014;25(3):281–288. doi:10.1016/j.jnutbio.2013.10.008
   Web of Science ®Google Scholar
• Newton AC. Protein kinase C: poised to signal. Am J Physiol Endocrinol Metab. 2010;298(3):E395–E402. doi:10.1152/ajpendo.00477.2009
   PubMed Web of Science ®Google Scholar
• Giorgione JR, Lin JH, McCammon JA, et al. Increased membrane affinity of the C1 domain of protein kinase Cdelta compensates for the lack of involvement of its C2 domain in membrane recruitment. J Biol Chem. 2006;281(3):1660–1669. doi:10.1074/jbc.M510251200
   PubMed Web of Science ®Google Scholar
• Samuel VT, Liu ZX, Qu X, et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004;279(31):32345–32353. doi:10.1074/jbc.M313478200
   PubMed Web of Science ®Google Scholar
• Lee SJ, Kang JH, Choi SY, et al. PKCδ as a regulator for TGFβ1-induced α-SMA production in a murine nonalcoholic steatohepatitis model. PLoS One. 2013;8(2):e55979. doi:10.1371/journal.pone.0055979
   Web of Science ®Google Scholar
• Badi RM, Mostafa DG, Khaleel EF, et al. Resveratrol protects against hepatic insulin resistance in a rat’s model of non-alcoholic fatty liver disease by down-regulation of GPAT-1 and DGAT2 expression and inhibition of PKC membranous translocation. Clin Exp Pharmacol Physiol. 2019;46(6):545–555. doi:10.1111/1440-1681.13074
   Web of Science ®Google Scholar
• Samidurai M, Palanisamy BN, Bargues-Carot A, et al. PKC Delta Activation Promotes Endoplasmic Reticulum Stress (ERS) and NLR Family Pyrin Domain-Containing 3 (NLRP3) Inflammasome Activation Subsequent to Asynuclein-Induced Microglial Activation: involvement of Thioredoxin-Interacting Protein (TXNIP)/Thioredoxin (Trx) Redoxisome Pathway. Front Aging Neurosci. 2021;13:661505. doi:10.3389/fnagi.2021.661505
   Web of Science ®Google Scholar
• Jornayvaz FR, Birkenfeld AL, Jurczak MJ, et al. Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2. Proc Natl Acad Sci U S A. 2011;108(14):5748–5752. doi:10.1073/pnas.1103451108
   PubMed Web of Science ®Google Scholar
• Dallak MA. Acylated ghrelin induces but deacylated ghrelin prevents hepatic steatosis and insulin resistance in lean rats: effects on DAG/ PKC/JNK pathway. Biomed Pharmacother. 2018;105:299–311. doi:10.1016/j.biopha.2018.05.098
   PubMed Web of Science ®Google Scholar
• Frangioudakis G, Burchfield JG, Narasimhan S, et al. Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta. Diabetologia. 2009;52(12):2616–2620. doi:10.1007/s00125-009-1543-0
   Web of Science ®Google Scholar
• Zhang J, Burrington CM, Davenport SK, et al. PKCδ regulates hepatic triglyceride accumulation and insulin signaling in Lepr(db/db) mice. Biochem Biophys Res Commun. 2014;450(4):1619–1625. doi:10.1016/j.bbrc.2014.07.048
   Web of Science ®Google Scholar
• Samuel VT, Liu ZX, Wang A, et al. Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest. 2007;117(3):739–745. doi:10.1172/JCI30400
   Web of Science ®Google Scholar
• Greene MW, Burrington CM, Lynch DT, et al. Lipid metabolism, oxidative stress and cell death are regulated by PKC delta in a dietary model of nonalcoholic steatohepatitis. PLoS One. 2014;9(1):e85848. doi:10.1371/journal.pone.0085848
   Web of Science ®Google Scholar
• Klymenko K, Novokhatska T, Kizub I, et al.. PKC-δ isozyme gene silencing restores vascular function in diabetic rat. J Basic Clin Physiol Pharmacol. 2014:1–9. doi:10.1515/jbcpp-2013-0147
   Google Scholar
• Pereira S, Park E, Mori Y, et al. FFA-induced hepatic insulin resistance in vivo is mediated by PKCδ, NADPH oxidase, and oxidative stress. Am J Physiol Endocrinol Metab. 2014;307(1):E34–E46. doi:10.1152/ajpendo.00436.2013
   Web of Science ®Google Scholar
• De Mattia G, Bravi MC, Laurenti O, et al. Influence of reduced glutathione infusion on glucose metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism. 1998;47(8):993–997. doi:10.1016/s0026-0495(98)90357-2
   Web of Science ®Google Scholar
• Zhang XQ, Xu CF, Yu CH, et al. Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(7):1768–1776. doi:10.3748/wjg.v20.i7.1768
   PubMed Web of Science ®Google Scholar
• Yang M, Chen Z, Xiang S, et al. Hugan Qingzhi medication ameliorates free fatty acid-induced L02 hepatocyte endoplasmic reticulum stress by regulating the activation of PKC-δ. BMC Complement Med Ther. 2020;20(1):377. doi:10.1186/s12906-020-03164-3
   Google Scholar
• Greene MW, Burrington CM, Ruhoff MS, et al. PKC{delta} is activated in a dietary model of steatohepatitis and regulates endoplasmic reticulum stress and cell death. J Biol Chem. 2010;285(53):42115–42129. doi:10.1074/jbc.M110.168575
   Web of Science ®Google Scholar
• Wang H, Chakrabarty S. Platelet-activating factor activates mitogen-activated protein kinases, inhibits proliferation, induces differentiation and suppresses the malignant phenotype of human colon carcinoma cells. Oncogene. 2003;22(14):2186–2191. doi:10.1038/sj.onc.1206348
   Web of Science ®Google Scholar
• Yu SM, Tsai SY, Kuo SC, et al. Inhibition of platelet function by A02131-1, a novel inhibitor of cGMP-specific phosphodiesterase, in vitro and in vivo. Blood. 1996;87(9):3758–3767.
   Web of Science ®Google Scholar
• Richardson L, Dixon CL, Aguilera-Aguirre L, et al. Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells. Biol Reprod. 2018;99(5):1100–1112. doi:10.1093/biolre/ioy135
   Web of Science ®Google Scholar
• Liu YM, Wang X, Nawaz A, et al. Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway. Acta Pharmacol Sin. 2011;32(12):1475–1482. doi:10.1038/aps.2011.120
   Web of Science ®Google Scholar
• Inoguchi T, Li P, Umeda F, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C–dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49(11):1939–1945. doi:10.2337/diabetes.49.11.1939
   PubMed Web of Science ®Google Scholar
• Niu W, Huang C, Nawaz Z, et al. Maturation of the regulation of GLUT4 activity by p38 MAPK during L6 cell myogenesis. J Biol Chem. 2003;278(20):17953–17962. doi:10.1074/jbc.M211136200
   Web of Science ®Google Scholar
• Hong F, Wu N, Ge Y, et al. Nanosized titanium dioxide resulted in the activation of TGF-β/Smads/p38MAPK pathway in renal inflammation and fibration of mice. J Biomed Mater Res A. 2016;104(6):1452–1461. doi:10.1002/jbm.a.35678
   Web of Science ®Google Scholar
• Leelahavanichkul K, Amornphimoltham P, Molinolo AA, et al. A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis. Mol Oncol. 2014;8(1):105–118. doi:10.1016/j.molonc.2013.10.003
   PubMed Web of Science ®Google Scholar
• Gao W, Du X, Lei L, et al. NEFA-induced ROS impaired insulin signalling through the JNK and p38MAPK pathways in non-alcoholic steatohepatitis. J Cell Mol Med. 2018;22(7):3408–3422. doi:10.1111/jcmm.13617
   PubMed Web of Science ®Google Scholar
• Wang W, Li X, Xu J. Magnesium isoglycyrrhizinate attenuates D-galactosamine/lipopolysaccharides induced acute liver injury of rat via regulation of the p38-MAPK and NF-κB signaling pathways. Immunopharmacol Immunotoxicol. 2018;40(3):262–267. doi:10.1080/08923973.2018.1441300
   PubMed Web of Science ®Google Scholar
• Tang Z, Xia N, Yuan X, et al. PRDX1 is involved in palmitate induced insulin resistance via regulating the activity of p38MAPK in HepG2 cells. Biochem Biophys Res Commun. 2015;465(4):670–677. doi:10.1016/j.bbrc.2015.08.008
   PubMed Web of Science ®Google Scholar
• Liu Y, Song A, Zang S, et al. Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high-fat fed rats. J Ethnopharmacol. 2015;162:244–252. doi:10.1016/j.jep.2014.12.040
   PubMed Web of Science ®Google Scholar
• Zhu Y, Zhang H, Wei Y, et al. Pea-derived peptides, VLP, LLP, VA, and LL, improve insulin resistance in HepG2 cells via activating IRS-1/PI3K/AKT and blocking ROS-mediated p38MAPK signaling. J Food Biochem. 2020;44(11):e13454. doi:10.1111/jfbc.13454
   Web of Science ®Google Scholar
• Gong XW, Xu YJ, Yang QH, et al. Effect of soothing gan (liver) and invigorating Pi (spleen) recipes on TLR4-p38 MAPK pathway in kupffer cells of non-alcoholic steatohepatitis rats. Chin J Integr Med. 2019;25(3):216–224. doi:10.1007/s11655-018-2829-6
   Web of Science ®Google Scholar
• Zhang HA, Yang XY, Xiao YF. AMPKα1 overexpression alleviates the hepatocyte model of nonalcoholic fatty liver disease via inactivating p38MAPK pathway. Biochem Biophys Res Commun. 2016;474(2):364–370. doi:10.1016/j.bbrc.2016.04.111
   Web of Science ®Google Scholar
• Böhm T, Berger H, Nejabat M, et al. Food-derived peroxidized fatty acids may trigger hepatic inflammation: a novel hypothesis to explain steatohepatitis. J Hepatol. 2013;59(3):563–570. doi:10.1016/j.jhep.2013.04.025
   Web of Science ®Google Scholar
• Luo Y, Tian G, Zhuang Z, et al. Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice. Am J Transl Res. 2019;11(5):2668–2682.
   PubMed Web of Science ®Google Scholar
• Ceccarelli S, Panera N, Mina M, et al. LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease. Oncotarget. 2015;6(39):41434–41452. doi:10.18632/oncotarget.5163
   Google Scholar
• Zhao ZB, Ji K, Shen XY, et al. Di(2-ethylhexyl) phthalate promotes hepatic fibrosis by regulation of oxidative stress and inflammation responses in rats. Environ Toxicol Pharmacol. 2019;68:109–119. doi:10.1016/j.etap.2019.03.008
   Web of Science ®Google Scholar