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Obesity and nonalcoholic fatty liver disease: current perspectives. Diabetes Metab. Syndr. Obes.<\/i>, 11<\/b>, 533\u2013542 (2018).","DOI":"10.2147\/DMSO.S146339"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Gao B, Bataller R. Alcoholic liver disease: Pathogenesis and new therapeutic targets. Gastroenterology<\/i>, 141<\/b>, 1572\u20131585 (2011).","DOI":"10.1053\/j.gastro.2011.09.002"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Donohue TM Jr. Alcohol-induced steatosis in liver cells. World J. Gastroenterol.<\/i>, 13<\/b>, 4974\u20134978 (2007).","DOI":"10.3748\/wjg.v13.i37.4974"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Zeng T, Zhang C-L, Zhao N, Guan M-J, Xiao M, Yang R, Zhao X-L, Yu L-H, Zhu Z-P, Xie K-Q. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver. Redox Biol.<\/i>, 14<\/b>, 295\u2013304 (2018).","DOI":"10.1016\/j.redox.2017.09.018"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) An L, Wang X, Cederbaum AI. Cytokines in alcoholic liver disease. Arch. Toxicol.<\/i>, 86<\/b>, 1337\u20131348 (2012).","DOI":"10.1007\/s00204-012-0814-6"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Tilg H, Moschen AR, Kaneider NC. Pathways of liver injury in alcoholic liver disease. J. Hepatol.<\/i>, 55<\/b>, 1159\u20131161 (2011).","DOI":"10.1016\/j.jhep.2011.05.015"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Lieber CS. Alcoholic fatty liver: Its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol<\/i>, 34<\/b>, 9\u201319 (2004).","DOI":"10.1016\/j.alcohol.2004.07.008"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Setshedi M, Wands JR, de la Monte SM. Acetaldehyde adducts in alcoholic liver disease. Oxid. Med. Cell. Longev.<\/i>, 3<\/b>, 178\u2013185 (2010).","DOI":"10.4161\/oxim.3.3.12288"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Seth D, Haber PS, Syn W-K, Diehl AM, Day CP. Pathogenesis of alcohol-induced liver disease: classical concepts and recent advances. J. Gastroenterol. Hepatol.<\/i>, 26<\/b>, 1089\u20131105 (2011).","DOI":"10.1111\/j.1440-1746.2011.06756.x"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Longato L, Ripp K, Setshedi M, Dostalek M, Akhlaghi F, Branda M, Wands JR, de la Monte SM. Insulin resistance, ceramide accumulation, and endoplasmic reticulum stress in human chronic alcohol-related liver disease. Oxid. Med. Cell. Longev.<\/i>, 2012<\/b>, 479348 (2012).","DOI":"10.1155\/2012\/479348"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) DeNucci SM, Tong M, Longato L, Lawton M, Setshedi M, Carlson RI, Wands JR, de la Monte SM. Rat strain differences in susceptibility to alcohol-induced chronic liver injury and hepatic insulin resistance. Gastroenterol. Res. Pract.<\/i>, 2010<\/b>, 312790 (2010).","DOI":"10.1155\/2010\/312790"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Pang M, de la Monte SM, Longato L, Tong M, He J, Chaudhry R, Duan K, Ouh J, Wands JR. PPAR\u03b4 agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair. J. Hepatol.<\/i>, 50<\/b>, 1192\u20131201 (2009).","DOI":"10.1016\/j.jhep.2009.01.021"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Ronis MJJ, Wands JR, Badger TM, de la Monte SM, Lang CH, Calissendorff J. Alcohol-induced disruption of endocrine signaling. Alcohol. Clin. Exp. Res.<\/i>, 31<\/b>, 1269\u20131285 (2007).","DOI":"10.1111\/j.1530-0277.2007.00436.x"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Sasaki Y, Wands JR. Ethanol impairs insulin receptor substrate-1 mediated signal transduction during rat liver regeneration. Biochem. Biophys. Res. Commun.<\/i>, 199<\/b>, 403\u2013409 (1994).","DOI":"10.1006\/bbrc.1994.1243"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Setshedi M, Longato L, Petersen DR, Ronis M, Chen WC, Wands JR, de la Monte SM. Limited therapeutic effect of N-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis. Alcohol. Clin. Exp. Res.<\/i>, 35<\/b>, 2139\u20132151 (2011).","DOI":"10.1111\/j.1530-0277.2011.01569.x"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) de la Monte SM, Yeon J-E, Tong M, Longato L, Chaudhry R, Pang M-Y, Duan K, Wands JR. Insulin resistance in experimental alcohol-induced liver disease. J. Gastroenterol. Hepatol.<\/i>, 23<\/b>, e477\u2013e486 (2008).","DOI":"10.1111\/j.1440-1746.2008.05339.x"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Bruha R, Dvorak K, Petrtyl J. Alcoholic liver disease. World J. Hepatol.<\/i>, 4<\/b>, 81\u201390 (2012).","DOI":"10.4254\/wjh.v4.i3.81"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Woo GA, O\u2019Brien C. Long-term management of alcoholic liver disease. Clin. Liver Dis.<\/i>, 16<\/b>, 763\u2013781 (2012).","DOI":"10.1016\/j.cld.2012.08.007"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Thomes PG, Rasineni K, Yang L, Donohue TM Jr, Kubik JL, McNiven MA, Casey CA. Ethanol withdrawal mitigates fatty liver by normalizing lipid catabolism. Am. J. Physiol. Gastrointest. Liver Physiol.<\/i>, 316<\/b>, G509\u2013G518 (2019).","DOI":"10.1152\/ajpgi.00376.2018"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Szabo G. Gut-liver axis in alcoholic liver disease. Gastroenterology<\/i>, 148<\/b>, 30\u201336 (2015).","DOI":"10.1053\/j.gastro.2014.10.042"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Shearer BG, Hoekstra W. Recent advances in peroxisome proliferator-activated receptor science. Curr. Med. Chem.<\/i>, 10<\/b>, 267\u2013280 (2003).","DOI":"10.2174\/0929867033368295"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Nuclear Receptors Nomenclature Committee. A unified nomenclature system for the nuclear receptor superfamily. Cell<\/i>, 97<\/b>, 161\u2013163 (1999).","DOI":"10.1016\/S0092-8674(00)80726-6"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Smith SA. Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism. Biochem. Soc. Trans.<\/i>, 30<\/b>, 1086\u20131090 (2002).","DOI":"10.1042\/bst0301086"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Peters JM, Shah YM, Gonzalez FJ. The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat. Rev. Cancer<\/i>, 12<\/b>, 181\u2013195 (2012).","DOI":"10.1038\/nrc3214"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-\u03b1 in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes<\/i>, 46<\/b>, 1319\u20131327 (1997).","DOI":"10.2337\/diab.46.8.1319"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Braissant O, Foufelle F, Scotto C, Dau\u00e7a M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-\u03b1, -\u03b2, and -\u03b3 in the adult rat. Endocrinology<\/i>, 137<\/b>, 354\u2013366 (1996).","DOI":"10.1210\/endo.137.1.8536636"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Girroir EE, Hollingshead HE, He P, Zhu B, Perdew GH, Peters JM. Quantitative expression patterns of peroxisome proliferator-activated receptor-\u03b2\/\u03b4 (PPAR\u03b2\/\u03b4) protein in mice. Biochem. Biophys. Res. Commun.<\/i>, 371<\/b>, 456\u2013461 (2008).","DOI":"10.1016\/j.bbrc.2008.04.086"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Escher P, Braissant O, Basu-Modak S, Michalik L, Wahli W, Desvergne B. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology<\/i>, 142<\/b>, 4195\u20134202 (2001).","DOI":"10.1210\/endo.142.10.8458"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Khozoie C, Borland MG, Zhu B, Baek S, John S, Hager GL, Shah YM, Gonzalez FJ, Peters JM. Analysis of the peroxisome proliferator-activated receptor-\u03b2\/\u03b4 (PPAR\u03b2\/\u03b4) cistrome reveals novel co-regulatory role of ATF4. BMC Genomics<\/i>, 13<\/b>, 665 (2012).","DOI":"10.1186\/1471-2164-13-665"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog. Lipid Res.<\/i>, 45<\/b>, 120\u2013159 (2006).","DOI":"10.1016\/j.plipres.2005.12.002"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Lefebvre P, Chinetti G, Fruchart J-C, Staels B. Sorting out the roles of PPAR\u03b1 in energy metabolism and vascular homeostasis. J. Clin. Invest.<\/i>, 116<\/b>, 571\u2013580 (2006).","DOI":"10.1172\/JCI27989"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Vidal-Puig A, Jimenez-Li\u00f1an M, Lowell BB, Hamann A, Hu E, Spiegelman B, Flier JS, Moller DE. Regulation of PPAR \u03b3 gene expression by nutrition and obesity in rodents. J. Clin. Invest.<\/i>, 97<\/b>, 2553\u20132561 (1996).","DOI":"10.1172\/JCI118703"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Mello T, Polvani S, Galli A. Peroxisome proliferator-activated receptor and retinoic X receptor in alcoholic liver disease. PPAR Res.<\/i>, 2009<\/b>, 748174 (2009).","DOI":"10.1155\/2009\/748174"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Wan YJ, Morimoto M, Thurman RG, Bojes HK, French SW. Expression of the peroxisome proliferator-activated receptor gene is decreased in experimental alcoholic liver disease. Life Sci.<\/i>, 56<\/b>, 307\u2013317 (1995).","DOI":"10.1016\/0024-3205(94)00953-8"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Zeng T, Zhang C-L, Song F-Y, Zhao X-L, Xie K-Q. CMZ reversed chronic ethanol-induced disturbance of PPAR-\u03b1 possibly by suppressing oxidative stress and PGC-1\u03b1 acetylation, and activating the MAPK and GSK3\u03b2 pathway. PLOS ONE<\/i>, 9<\/b>, e98658 (2014).","DOI":"10.1371\/journal.pone.0098658"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Lu Y, Zhuge J, Wang X, Bai J, Cederbaum AI. Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice. Hepatology<\/i>, 47<\/b>, 1483\u20131494 (2008).","DOI":"10.1002\/hep.22222"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Wang Y, Zhao Y, Li M, Wang Y, Yu S, Zeng T. Docosahexaenoic acid supplementation failed to attenuate chronic alcoholic fatty liver in mice. Acta Biochim. Biophys. Sin. <\/i>(Shanghai), 48<\/b>, 482\u2013484 (2016).","DOI":"10.1093\/abbs\/gmw016"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Chen Y-Y, Zhang C-L, Zhao X-L, Xie K-Q, Zeng T. Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver. Chem. Biol. Interact.<\/i>, 222<\/b>, 18\u201326 (2014).","DOI":"10.1016\/j.cbi.2014.08.009"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Li M, Diao Y, Liu Y, Huang H, Li Y, Tan P, Liang H, He Q, Nie J, Dong X, Wang Y, Zhou L, Gao X. Chronic moderate alcohol intakes accelerate SR-B1 mediated reverse cholesterol transport. Sci. Rep.<\/i>, 6<\/b>, 33032 (2016).","DOI":"10.1038\/srep33032"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) You M, Crabb DW. Recent advances in alcoholic liver disease II. Minireview: molecular mechanisms of alcoholic fatty liver. Am. J. Physiol. Gastrointest. Liver Physiol.<\/i>, 287<\/b>, G1\u2013G6 (2004).","DOI":"10.1152\/ajpgi.00056.2004"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Crabb DW, Liangpunsakul S. Alcohol and lipid metabolism. J. Gastroenterol. Hepatol.<\/i>, 21<\/b> (Suppl 3), S56\u2013S60 (2006).","DOI":"10.1111\/j.1440-1746.2006.04582.x"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Meng F-G, Zhang X-N, Liu S-X, Wang Y-R, Zeng T. Roles of peroxisome proliferator-activated receptor \u03b1 in the pathogenesis of ethanol-induced liver disease. Chem. Biol. Interact.<\/i>, 327<\/b>, 109176 (2020).","DOI":"10.1016\/j.cbi.2020.109176"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Jeon S, Carr R. Alcohol effects on hepatic lipid metabolism. J. Lipid Res.<\/i>, 61<\/b>, 470\u2013479 (2020).","DOI":"10.1194\/jlr.R119000547"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Fischer M, You M, Matsumoto M, Crabb DW. Peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) agonist treatment reverses PPAR\u03b1 dysfunction and abnormalities in hepatic lipid metabolism in ethanol-fed mice. J. Biol. Chem.<\/i>, 278<\/b>, 27997\u201328004 (2003).","DOI":"10.1074\/jbc.M302140200"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45) Nakajima T, Kamijo Y, Tanaka N, Sugiyama E, Tanaka E, Kiyosawa K, Fukushima Y, Peters JM, Gonzalez FJ, Aoyama T. Peroxisome proliferator-activated receptor \u03b1 protects against alcohol-induced liver damage. Hepatology<\/i>, 40<\/b>, 972\u2013980 (2004).","DOI":"10.1002\/hep.1840400428"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46) Galli A, Pinaire J, Fischer M, Dorris R, Crabb DW. The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor \u03b1 is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver. J. Biol. Chem.<\/i>, 276<\/b>, 68\u201375 (2001).","DOI":"10.1074\/jbc.M008791200"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47) Abdelmegeed MA, Moon K-H, Hardwick JP, Gonzalez FJ, Song BJ. Role of peroxisome proliferator-activated receptor-\u03b1 in fasting-mediated oxidative stress. Free Radic. Biol. Med.<\/i>, 47<\/b>, 767\u2013778 (2009).","DOI":"10.1016\/j.freeradbiomed.2009.06.017"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48) Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm. Res.<\/i>, 49<\/b>, 497\u2013505 (2000).","DOI":"10.1007\/s000110050622"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49) Wahli W, Michalik L. PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol. Metab.<\/i>, 23<\/b>, 351\u2013363 (2012).","DOI":"10.1016\/j.tem.2012.05.001"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50) Pyper SR, Viswakarma N, Yu S, Reddy JK. PPARalpha: energy combustion, hypolipidemia, inflammation and cancer. Nucl. Recept. Signal.<\/i>, 8<\/b>, nrs.08002 (2010).","DOI":"10.1621\/nrs.08002"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51) Kong L, Ren W, Li W, Zhao S, Mi H, Wang R, Zhang Y, Wu W, Nan Y, Yu J. Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepatitis in mice. Lipids Health Dis.<\/i>, 10<\/b>, 246 (2011).","DOI":"10.1186\/1476-511X-10-246"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52) Gavrilova O, Haluzik M, Matsusue K, Cutson JJ, Johnson L, Dietz KR, Nicol CJ, Vinson C, Gonzalez FJ, Reitman ML. Liver peroxisome proliferator-activated receptor g contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J. Biol. Chem.<\/i>, 278<\/b>, 34268\u201334276 (2003).","DOI":"10.1074\/jbc.M300043200"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53) Matsusue K, Haluzik M, Lambert G, Yim S-H, Gavrilova O, Ward JM, Brewer B Jr, Reitman ML, Gonzalez FJ. Liver-specific disruption of PPAR\u03b3 in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J. Clin. Invest.<\/i>, 111<\/b>, 737\u2013747 (2003).","DOI":"10.1172\/JCI200317223"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54) Skat-R\u00f8rdam J, H\u00f8jland Ipsen D, Lykkesfeldt J, Tveden-Nyborg P. A role of peroxisome proliferator-activated receptor \u03b3 in non-alcoholic fatty liver disease. Basic Clin. Pharmacol. Toxicol.<\/i>, 124<\/b>, 528\u2013537 (2019).","DOI":"10.1111\/bcpt.13190"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55) Schadinger SE, Bucher NLR, Schreiber BM, Farmer SR. PPAR\u03b32 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am. J. Physiol. Endocrinol. Metab.<\/i>, 288<\/b>, E1195\u2013E1205 (2005).","DOI":"10.1152\/ajpendo.00513.2004"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56) Chao L, Marcus-Samuels B, Mason MM, Moitra J, Vinson C, Arioglu E, Gavrilova O, Reitman ML. Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. J. Clin. Invest.<\/i>, 106<\/b>, 1221\u20131228 (2000).","DOI":"10.1172\/JCI11245"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57) Bedoucha M, Atzpodien E, Boelsterli UA. Diabetic KKAy mice exhibit increased hepatic PPAR\u03b31 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones. J. Hepatol.<\/i>, 35<\/b>, 17\u201323 (2001).","DOI":"10.1016\/S0168-8278(01)00066-6"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58) Rahimian R, Masih-Khan E, Lo M, Van Breemen C, McManus BM, Dub\u00e9 GP. Hepatic over-expression of peroxisome proliferator activated receptor \u03b32 in the ob\/ob mouse model of non-insulin dependent diabetes mellitus. Mol. Cell. Biochem.<\/i>, 224<\/b>, 29\u201337 (2001).","DOI":"10.1023\/A:1011927113563"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59) Zhang W, Sun Q, Zhong W, Sun X, Zhou Z. Hepatic peroxisome proliferator-activated receptor gamma signaling contributes to alcohol-induced hepatic steatosis and inflammation in mice. Alcohol. Clin. Exp. Res.<\/i>, 40<\/b>, 988\u2013999 (2016).","DOI":"10.1111\/acer.13049"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60) Yu JH, Song SJ, Kim A, Choi Y, Seok JW, Kim HJ, Lee YJ, Lee KS, Kim J. Suppression of PPAR\u03b3-mediated monoacylglycerol O<\/i>-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis. Sci. Rep.<\/i>, 6<\/b>, 29352 (2016).","DOI":"10.1038\/srep29352"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61) Ramirez T, Tong M, Ayala CA, Monfils PR, McMillan PN, Zabala V, Wands JR, de la Monte SM. Structural correlates of PPAR agonist rescue of experimental chronic alcohol-induced steatohepatitis. J. Clin. Exp. Pathol.<\/i>, 2<\/b>, 114 (2012).","DOI":"10.4172\/2161-0681.1000114"},{"key":"62","doi-asserted-by":"crossref","unstructured":"62) Liu X, Wang Y, Wu D, Li S, Wang C, Han Z, Wang J, Wang K, Yang Z, Wei Z. Magnolol prevents acute alcoholic liver damage by activating PI3K\/Nrf2\/PPAR\u03b3 and inhibiting NLRP3 signaling pathway. Front. Pharmacol.<\/i>, 10<\/b>, 1459 (2019).","DOI":"10.3389\/fphar.2019.01459"},{"key":"63","doi-asserted-by":"crossref","unstructured":"63) Shan W, Nicol CJ, Ito S, Bility MT, Kennett MJ, Ward JM, Gonzalez FJ, Peters JM. Peroxisome proliferator-activated receptor-\u03b2\/\u03b4 protects against chemically induced liver toxicity in mice. Hepatology<\/i>, 47<\/b>, 225\u2013235 (2008).","DOI":"10.1002\/hep.21925"},{"key":"64","doi-asserted-by":"crossref","unstructured":"64) Shan W, Palkar PS, Murray IA, Mcdevitt EI, Kennett MJ, Kang BH, Isom HC, Perdew GH, Gonzalez FJ, Peters JM. Ligand activation of peroxisome proliferator-activated receptor \u03b2\/\u03b4 (PPAR\u03b2\/\u03b4) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression. Toxicol. Sci.<\/i>, 105<\/b>, 418\u2013428 (2008).","DOI":"10.1093\/toxsci\/kfn142"},{"key":"65","doi-asserted-by":"crossref","unstructured":"65) Bojic LA, Telford DE, Fullerton MD, Ford RJ, Sutherland BG, Edwards JY, Sawyez CG, Gros R, Kemp BE, Steinberg GR, Huff MW. PPAR\u03b4 activation attenuates hepatic steatosis in Ldlr\u2212\/\u2212<\/sup> mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity. J. Lipid Res.<\/i>, 55<\/b>, 1254\u20131266 (2014).","DOI":"10.1194\/jlr.M046037"},{"key":"66","doi-asserted-by":"crossref","unstructured":"66) Zarei M, Aguilar-Recarte D, Palomer X, V\u00e1zquez-Carrera M. Revealing the role of peroxisome proliferator-activated receptor \u03b2\/\u03b4 in nonalcoholic fatty liver disease. Metabolism<\/i>, 114<\/b>, 154342 (2021).","DOI":"10.1016\/j.metabol.2020.154342"},{"key":"67","doi-asserted-by":"crossref","unstructured":"67) Lieber CS, Savolainen M. Ethanol and lipids. Alcohol. Clin. Exp. Res.<\/i>, 8<\/b>, 409\u2013423 (1984).","DOI":"10.1111\/j.1530-0277.1984.tb05689.x"},{"key":"68","doi-asserted-by":"crossref","unstructured":"68) Carrasco MP, Jim\u00e9nez-L\u00f3pez JM, Segovia JL, Marco C. Comparative study of the effects of short- and long-term ethanol treatment and alcohol withdrawal on phospholipid biosynthesis in rat hepatocytes. Comp. Biochem. Physiol. B Biochem. Mol. Biol.<\/i>, 131<\/b>, 491\u2013497 (2002).","DOI":"10.1016\/S1096-4959(02)00006-4"},{"key":"69","doi-asserted-by":"crossref","unstructured":"69) Carrasco MP, Marco C, Segovia JL. Chronic ingestion of ethanol stimulates lipogenic response in rat hepatocytes. Life Sci.<\/i>, 68<\/b>, 1295\u20131304 (2001).","DOI":"10.1016\/S0024-3205(00)01035-3"},{"key":"70","doi-asserted-by":"crossref","unstructured":"70) Horton JD, Shimomura I, Brown MS, Hammer RE, Goldstein JL, Shimano H. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2. J. Clin. Invest.<\/i>, 101<\/b>, 2331\u20132339 (1998).","DOI":"10.1172\/JCI2961"},{"key":"71","doi-asserted-by":"crossref","unstructured":"71) Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J. Clin. Invest.<\/i>, 98<\/b>, 1575\u20131584 (1996).","DOI":"10.1172\/JCI118951"},{"key":"72","doi-asserted-by":"crossref","unstructured":"72) Qin X, Xie X, Fan Y, Tian J, Guan Y, Wang X, Zhu Y, Wang N. Peroxisome proliferator-activated receptor-\u03b4 induces insulin-induced gene-1 and suppresses hepatic lipogenesis in obese diabetic mice. Hepatology<\/i>, 48<\/b>, 432\u2013441 (2008).","DOI":"10.1002\/hep.22334"},{"key":"73","doi-asserted-by":"crossref","unstructured":"73) Goudarzi M, Koga T, Khozoie C, Mak TD, Kang BH, Fornace AJ Jr, Peters JM. PPAR\u03b2\/\u03b4 modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity. Toxicology<\/i>, 311<\/b>, 87\u201398 (2013).","DOI":"10.1016\/j.tox.2013.07.002"},{"key":"74","doi-asserted-by":"crossref","unstructured":"74) Ramirez T, Tong M, Chen WC, Nguyen Q-G, Wands JR, de la Monte SM. Chronic alcohol-induced hepatic insulin resistance and endoplasmic reticulum stress ameliorated by peroxisome-proliferator activated receptor-\u03b4 agonist treatment. J. Gastroenterol. Hepatol.<\/i>, 28<\/b>, 179\u2013187 (2013).","DOI":"10.1111\/j.1440-1746.2012.07256.x"},{"key":"75","doi-asserted-by":"crossref","unstructured":"75) de la Monte SM, Pang M, Chaudhry R, Duan K, Longato L, Carter J, Ouh J, Wands JR. Peroxisome proliferator-activated receptor agonist treatment of alcohol-induced hepatic insulin resistance. Hepatol. Res.<\/i>, 41<\/b>, 386\u2013398 (2011).","DOI":"10.1111\/j.1872-034X.2011.00775.x"},{"key":"76","doi-asserted-by":"crossref","unstructured":"76) Peters JM, Cheung C, Gonzalez FJ. Peroxisome proliferator-activated receptor-alpha and liver cancer: where do we stand? J. Mol. Med. <\/i>(Berl.), 83<\/b>, 774\u2013785 (2005).","DOI":"10.1007\/s00109-005-0678-9"},{"key":"77","doi-asserted-by":"crossref","unstructured":"77) Peraza MA, Burdick AD, Marin HE, Gonzalez FJ, Peters JM. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicol. Sci.<\/i>, 90<\/b>, 269\u2013295 (2006).","DOI":"10.1093\/toxsci\/kfj062"},{"key":"78","doi-asserted-by":"crossref","unstructured":"78) Neels JG, Grimaldi PA. Physiological functions of peroxisome proliferator-activated receptor \u03b2. Physiol. Rev.<\/i>, 94<\/b>, 795\u2013858 (2014).","DOI":"10.1152\/physrev.00027.2013"},{"key":"79","doi-asserted-by":"crossref","unstructured":"79) Rakhshandehroo M, Knoch B, M\u00fcller M, Kersten S. Peroxisome Proliferator-Activated Receptor Alpha Target Genes. PPAR Res.<\/i>, 2010<\/b>, 612089 (2010).","DOI":"10.1155\/2010\/612089"},{"key":"80","doi-asserted-by":"crossref","unstructured":"80) Gutgesell A, Wen G, K\u00f6nig B, Koch A, Spielmann J, Stangl GI, Eder K, Ringseis R. Mouse carnitine-acylcarnitine translocase (CACT) is transcriptionally regulated by PPAR\u03b1 and PPAR\u03b4 in liver cells. Biochim. Biophys. Acta<\/i>, 1790<\/b>, 1206\u20131216 (2009).","DOI":"10.1016\/j.bbagen.2009.06.012"},{"key":"81","doi-asserted-by":"crossref","unstructured":"81) Houten SM, Wanders RJA. A general introduction to the biochemistry of mitochondrial fatty acid \u03b2-oxidation. J. Inherit. Metab. Dis.<\/i>, 33<\/b>, 469\u2013477 (2010).","DOI":"10.1007\/s10545-010-9061-2"},{"key":"82","doi-asserted-by":"crossref","unstructured":"82) Lee C-H, Olson P, Hevener A, Mehl I, Chong L-W, Olefsky JM, Gonzalez FJ, Ham J, Kang H, Peters JM, Evans RM. PPAR\u03b4 regulates glucose metabolism and insulin sensitivity. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 103<\/b>, 3444\u20133449 (2006).","DOI":"10.1073\/pnas.0511253103"},{"key":"83","doi-asserted-by":"crossref","unstructured":"83) Reilly SM, Lee C-H. PPAR\u03b4 as a therapeutic target in metabolic disease. FEBS Lett.<\/i>, 582<\/b>, 26\u201331 (2008).","DOI":"10.1016\/j.febslet.2007.11.040"},{"key":"84","doi-asserted-by":"crossref","unstructured":"84) Kr\u00e4mer DK, Al-Khalili L, Guigas B, Leng Y, Garcia-Roves PM, Krook A. Role of AMP kinase and PPAR\u03b4 in the regulation of lipid and glucose metabolism in human skeletal muscle. J. Biol. Chem.<\/i>, 282<\/b>, 19313\u201319320 (2007).","DOI":"10.1074\/jbc.M702329200"},{"key":"85","doi-asserted-by":"crossref","unstructured":"85) Barroso E, Rodr\u00edguez-Calvo R, Serrano-Marco L, Astudillo AM, Balsinde J, Palomer X, V\u00e1zquez-Carrera M. The PPAR\u03b2\/\u03b4 activator GW501516 prevents the down-regulation of AMPK caused by a high-fat diet in liver and amplifies the PGC-1\u03b1-L ipin 1-PPAR\u03b1 pathway leading to increased fatty acid oxidation. Endocrinology<\/i>, 152<\/b>, 1848\u20131859 (2011).","DOI":"10.1210\/en.2010-1468"},{"key":"86","doi-asserted-by":"crossref","unstructured":"86) Tong L, Wang L, Yao S, Jin L, Yang J, Zhang Y, Ning G, Zhang Z. PPAR\u03b4 attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation. Cell Death Dis.<\/i>, 10<\/b>, 197 (2019).","DOI":"10.1038\/s41419-019-1458-8"},{"key":"87","doi-asserted-by":"crossref","unstructured":"87) Ding W-X, Manley S, Ni H-M. The emerging role of autophagy in alcoholic liver disease. Exp. Biol. Med. <\/i>(Maywood), 236<\/b>, 546\u2013556 (2011).","DOI":"10.1258\/ebm.2011.010360"},{"key":"88","doi-asserted-by":"crossref","unstructured":"88) Menk M, Graw JA, Poyraz D, M\u00f6bius N, Spies CD, von Haefen C. Chronic alcohol consumption inhibits autophagy and promotes apoptosis in the liver. Int. J. Med. Sci.<\/i>, 15<\/b>, 682\u2013688 (2018).","DOI":"10.7150\/ijms.25393"},{"key":"89","doi-asserted-by":"crossref","unstructured":"89) Chao X, Ding W-X. Role and mechanisms of autophagy in alcohol-induced liver injury. Adv. Pharmacol.<\/i>, 85<\/b>, 109\u2013131 (2019).","DOI":"10.1016\/bs.apha.2019.01.008"},{"key":"90","doi-asserted-by":"crossref","unstructured":"90) Tang J-J, Li J-G, Qi W, Qiu W-W, Li P-S, Li B-L, Song B-L. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques. Cell Metab.<\/i>, 13<\/b>, 44\u201356 (2011).","DOI":"10.1016\/j.cmet.2010.12.004"},{"key":"91","doi-asserted-by":"crossref","unstructured":"91) Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb. Perspect. Biol.<\/i>, 6<\/b>, a009191 (2014).","DOI":"10.1101\/cshperspect.a009191"},{"key":"92","doi-asserted-by":"publisher","unstructured":"92) Sbraccia P, D\u2019Adamo M, Guglielmi V. Is type 2 diabetes an adiposity-based metabolic disease? From the origin of insulin resistance to the concept of dysfunctional adipose tissue. Eat. Weight Disord.<\/i>, (2021), in press. doi: 10.1007\/s40519-021-01109-4.","DOI":"10.1007\/s40519-021-01109-4"},{"key":"93","doi-asserted-by":"crossref","unstructured":"93) Rinaldi L, Pafundi PC, Galiero R, Caturano A, Morone MV, Silvestri C, Giordano M, Salvatore T, Sasso FC. Mechanisms of non-alcoholic fatty liver disease in the metabolic syndrome. A narrative review. Antioxidants<\/i>, 10<\/b>, 270 (2021).","DOI":"10.3390\/antiox10020270"},{"key":"94","doi-asserted-by":"crossref","unstructured":"94) Gerges SH, Wahdan SA, Elsherbiny DA, El-Demerdash E. Non-alcoholic fatty liver disease: an overview of risk factors, pathophysiological mechanisms, diagnostic procedures, and therapeutic interventions. Life Sci.<\/i>, 271<\/b>, 119220 (2021).","DOI":"10.1016\/j.lfs.2021.119220"},{"key":"95","doi-asserted-by":"crossref","unstructured":"95) Postic C, Girard J. Contribution of de novo<\/i> fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. Clin. Invest.<\/i>, 118<\/b>, 829\u2013838 (2008).","DOI":"10.1172\/JCI34275"},{"key":"96","doi-asserted-by":"crossref","unstructured":"96) Sanders FWB, Griffin JL. De novo<\/i> lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biol. Rev. Camb. Philos. Soc.<\/i>, 91<\/b>, 452\u2013468 (2016).","DOI":"10.1111\/brv.12178"},{"key":"97","doi-asserted-by":"crossref","unstructured":"97) Paulson QX, Hong J, Holcomb VB, Nunez NP. Effects of body weight and alcohol consumption on insulin sensitivity. Nutr. J.<\/i>, 9<\/b>, 14 (2010).","DOI":"10.1186\/1475-2891-9-14"},{"key":"98","doi-asserted-by":"crossref","unstructured":"98) Villegas R, Salim A, O\u2019Halloran D, Perry IJ. Alcohol intake and insulin resistance. A cross-sectional study. Nutr. Metab. Cardiovasc. Dis.<\/i>, 14<\/b>, 233\u2013240 (2004).","DOI":"10.1016\/S0939-4753(04)80049-8"},{"key":"99","doi-asserted-by":"crossref","unstructured":"99) Barron KA, Jeffries KA, Krupenko NI. Sphingolipids and the link between alcohol and cancer. Chem. Biol. Interact.<\/i>, 322<\/b>, 109058 (2020).","DOI":"10.1016\/j.cbi.2020.109058"},{"key":"100","doi-asserted-by":"crossref","unstructured":"100) Ramirez T, Longato L, Dostalek M, Tong M, Wands JR, de la Monte SM. Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in experimental chronic alcohol-induced steatohepatitis. Alcohol Alcohol.<\/i>, 48<\/b>, 39\u201352 (2013).","DOI":"10.1093\/alcalc\/ags106"},{"key":"101","doi-asserted-by":"crossref","unstructured":"101) Matsuzaka T, Kuba M, Koyasu S, et al.<\/i> Hepatocyte ELOVL fatty acid elongase 6 determines ceramide acyl-chain length and hepatic insulin sensitivity in mice. Hepatology<\/i>, 71<\/b>, 1609\u20131625 (2020).","DOI":"10.1002\/hep.30953"},{"key":"102","doi-asserted-by":"crossref","unstructured":"102) Carey AL, Febbraio MA. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia<\/i>, 47<\/b>, 1135\u20131142 (2004).","DOI":"10.1007\/s00125-004-1447-y"},{"key":"103","doi-asserted-by":"crossref","unstructured":"103) Klover PJ, Clementi AH, Mooney RA. Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology<\/i>, 146<\/b>, 3417\u20133427 (2005).","DOI":"10.1210\/en.2004-1468"},{"key":"104","doi-asserted-by":"crossref","unstructured":"104) Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes<\/i>, 52<\/b>, 2784\u20132789 (2003).","DOI":"10.2337\/diabetes.52.11.2784"},{"key":"105","doi-asserted-by":"crossref","unstructured":"105) Senn JJ, Klover PJ, Nowak IA, Zimmers TA, Koniaris LG, Furlanetto RW, Mooney RA. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J. Biol. Chem.<\/i>, 278<\/b>, 13740\u201313746 (2003).","DOI":"10.1074\/jbc.M210689200"},{"key":"106","doi-asserted-by":"crossref","unstructured":"106) Nerstedt A, Johansson A, Andersson CX, Cansby E, Smith U, Mahlapuu M. AMP-activated protein kinase inhibits IL-6-stimulated inflammatory response in human liver cells by suppressing phosphorylation of signal transducer and activator of transcription 3 (STAT3). Diabetologia<\/i>, 53<\/b>, 2406\u20132416 (2010).","DOI":"10.1007\/s00125-010-1856-z"},{"key":"107","doi-asserted-by":"crossref","unstructured":"107) Serrano-Marco L, Barroso E, El Kochairi I, Palomer X, Michalik L, Wahli W, V\u00e1zquez-Carrera M. The peroxisome proliferator-activated receptor (PPAR) \u03b2\/\u03b4 agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells. Diabetologia<\/i>, 55<\/b>, 743\u2013751 (2012).","DOI":"10.1007\/s00125-011-2401-4"},{"key":"108","doi-asserted-by":"crossref","unstructured":"108) Thomes PG, Donohue T. Role of early growth response-1 in the development of alcohol-induced steatosis. Curr. Mol. Pharmacol.<\/i>, 10<\/b>, 179\u2013185 (2017).","DOI":"10.2174\/1874467208666150817112529"},{"key":"109","doi-asserted-by":"crossref","unstructured":"109) Donohue TM Jr, Thomes PG. Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity. Redox Biol.<\/i>, 3<\/b>, 29\u201339 (2014).","DOI":"10.1016\/j.redox.2014.10.006"},{"key":"110","doi-asserted-by":"crossref","unstructured":"110) Lieber CS. Ethanol metabolism, cirrhosis and alcoholism. Clin. Chim. Acta<\/i>, 257<\/b>, 59\u201384 (1997).","DOI":"10.1016\/S0009-8981(96)06434-0"},{"key":"111","doi-asserted-by":"crossref","unstructured":"111) Teschke R, Gellert J. Hepatic microsomal ethanol-oxidizing system (MEOS): metabolic aspects and clinical implications. Alcohol. Clin. Exp. Res.<\/i>, 10<\/b> (Suppl.), 20S\u201332S (1986).","DOI":"10.1111\/j.1530-0277.1986.tb05176.x"},{"key":"112","doi-asserted-by":"crossref","unstructured":"112) Teschke R. Alcoholic liver disease: alcohol metabolism, cascade of molecular mechanisms, cellular targets, and clinical aspects. Biomedicines<\/i>, 6<\/b>, 106 (2018).","DOI":"10.3390\/biomedicines6040106"},{"key":"113","doi-asserted-by":"crossref","unstructured":"113) Jin M, Ande A, Kumar A, Kumar S. Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc\/jnk\/sp1 pathway. Cell Death Dis.<\/i>, 4<\/b>, e554 (2013).","DOI":"10.1038\/cddis.2013.78"},{"key":"114","doi-asserted-by":"crossref","unstructured":"114) Liu J. Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver. World J. Gastroenterol.<\/i>, 20<\/b>, 14672\u201314685 (2014).","DOI":"10.3748\/wjg.v20.i40.14672"},{"key":"115","doi-asserted-by":"crossref","unstructured":"115) Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ. J.<\/i>, 5<\/b>, 9\u201319 (2012).","DOI":"10.1097\/WOX.0b013e3182439613"},{"key":"116","doi-asserted-by":"crossref","unstructured":"116) Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic. Biol. Med.<\/i>, 44<\/b>, 723\u2013738 (2008).","DOI":"10.1016\/j.freeradbiomed.2007.11.004"},{"key":"117","doi-asserted-by":"crossref","unstructured":"117) Cederbaum AI. Role of CYP2E1 in ethanol-induced oxidant stress, fatty liver and hepatotoxicity. Dig. Dis.<\/i>, 28<\/b>, 802\u2013811 (2010).","DOI":"10.1159\/000324289"},{"key":"118","doi-asserted-by":"crossref","unstructured":"118) Schoedel KA, Sellers EM, Tyndale RF. Induction of CYP2B1\/2 and nicotine metabolism by ethanol in rat liver but not rat brain. Biochem. Pharmacol.<\/i>, 62<\/b>, 1025\u20131036 (2001).","DOI":"10.1016\/S0006-2952(01)00744-4"},{"key":"119","doi-asserted-by":"crossref","unstructured":"119) Dai T, Wu Y, Leng A-S, Ao Y, Robel RCV, Lu SC, French SW, Wan Y-JY. RXR\u03b1-regulated liver SAMe and GSH levels influence susceptibility to alcohol-induced hepatotoxicity. Exp. Mol. Pathol.<\/i>, 75<\/b>, 194\u2013200 (2003).","DOI":"10.1016\/S0014-4800(03)00091-1"},{"key":"120","doi-asserted-by":"crossref","unstructured":"120) Nelson DR, Zeldin DC, Hoffman SMG, Maltais LJ, Wain HM, Nebert DW. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics<\/i>, 14<\/b>, 1\u201318 (2004).","DOI":"10.1097\/00008571-200401000-00001"},{"key":"121","doi-asserted-by":"crossref","unstructured":"121) Damiri B, Holle E, Yu X, Baldwin WS. Lentiviral-mediated RNAi knockdown yields a novel mouse model for studying Cyp2b function. Toxicol. Sci.<\/i>, 125<\/b>, 368\u2013381 (2012).","DOI":"10.1093\/toxsci\/kfr309"},{"key":"122","doi-asserted-by":"crossref","unstructured":"122) Kumar R, Mota LC, Litoff EJ, Rooney JP, Boswell WT, Courter E, Henderson CM, Hernandez JP, Corton JC, Moore DD, Baldwin WS. Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9\/10\/13-null mice. PLOS ONE<\/i>, 12<\/b>, e0174355 (2017).","DOI":"10.1371\/journal.pone.0174355"},{"key":"123","doi-asserted-by":"crossref","unstructured":"123) Mota LC, Hernandez JP, Baldwin WS. Constitutive androstane receptor-null mice are sensitive to the toxic effects of parathion: association with reduced cytochrome P450-mediated parathion metabolism. Drug Metab. Dispos.<\/i>, 38<\/b>, 1582\u20131588 (2010).","DOI":"10.1124\/dmd.110.032961"},{"key":"124","doi-asserted-by":"crossref","unstructured":"124) Peng L, Yoo B, Gunewardena SS, Lu H, Klaassen CD, Zhong X-B. RNA sequencing reveals dynamic changes of mRNA abundance of cytochromes P450 and their alternative transcripts during mouse liver development. Drug Metab. Dispos.<\/i>, 40<\/b>, 1198\u20131209 (2012).","DOI":"10.1124\/dmd.112.045088"},{"key":"125","doi-asserted-by":"crossref","unstructured":"125) Oshida K, Vasani N, Jones C, Moore T, Hester S, Nesnow S, Auerbach S, Geter DR, Aleksunes LM, Thomas RS, Applegate D, Klaassen CD, Corton JC. Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium. Nucl. Recept. Signal.<\/i>, 13<\/b>, nrs.13002 (2015).","DOI":"10.1621\/nrs.13002"},{"key":"126","doi-asserted-by":"crossref","unstructured":"126) Hernandez JP, Mota LC, Huang W, Moore DD, Baldwin WS. Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR). Toxicology<\/i>, 256<\/b>, 53\u201364 (2009).","DOI":"10.1016\/j.tox.2008.11.002"},{"key":"127","doi-asserted-by":"crossref","unstructured":"127) Ding X, Staudinger JL. The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. J. Pharmacol. Exp. Ther.<\/i>, 314<\/b>, 120\u2013127 (2005).","DOI":"10.1124\/jpet.105.085225"},{"key":"128","doi-asserted-by":"crossref","unstructured":"128) Ding X, Lichti K, Kim I, Gonzalez FJ, Staudinger JL. Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor \u03b1, and the coactivator peroxisome proliferator-activated receptor \u03b3 coactivator-1\u03b1. J. Biol. Chem.<\/i>, 281<\/b>, 26540\u201326551 (2006).","DOI":"10.1074\/jbc.M600931200"},{"key":"129","doi-asserted-by":"crossref","unstructured":"129) Wang H, Negishi M. Transcriptional regulation of cytochrome P450 2B genes by nuclear receptors. Curr. Drug Metab.<\/i>, 4<\/b>, 515\u2013525 (2003).","DOI":"10.2174\/1389200033489262"},{"key":"130","doi-asserted-by":"crossref","unstructured":"130) Hernandez JP, Mota L, Baldwin W. Activation of CAR and PXR by dietary, environmental and occupational chemicals alters drug metabolism, intermediary metabolism, and cell proliferation. Curr. Pharmacogenomics Person. Med.<\/i>, 7<\/b>, 81\u2013105 (2009).","DOI":"10.2174\/187569209788654005"},{"key":"131","doi-asserted-by":"crossref","unstructured":"131) Honkakoski P, Zelko I, Sueyoshi T, Negishi M. The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol. Cell. Biol.<\/i>, 18<\/b>, 5652\u20135658 (1998).","DOI":"10.1128\/MCB.18.10.5652"},{"key":"132","doi-asserted-by":"crossref","unstructured":"132) Damiri B, Baldwin WS. Cyp2b-knockdown mice poorly metabolize corn oil and are age-dependent obese. Lipids<\/i>, 53<\/b>, 871\u2013884 (2018).","DOI":"10.1002\/lipd.12095"},{"key":"133","doi-asserted-by":"crossref","unstructured":"133) Finn RD, Henderson CJ, Scott CL, Wolf CR. Unsaturated fatty acid regulation of cytochrome P450 expression via<\/i> a CAR-dependent pathway. Biochem. J.<\/i>, 417<\/b>, 43\u201354 (2009).","DOI":"10.1042\/BJ20080740"},{"key":"134","doi-asserted-by":"crossref","unstructured":"134) Heintz MM, Kumar R, Rutledge MM, Baldwin WS. Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis. J. Nutr. Biochem.<\/i>, 70<\/b>, 125\u2013137 (2019).","DOI":"10.1016\/j.jnutbio.2019.05.004"},{"key":"135","doi-asserted-by":"crossref","unstructured":"135) Koga T, Yao P-L, Goudarzi M, Murray IA, Balandaram G, Gonzalez FJ, Perdew GH, Fornace AJ Jr, Peters JM. Regulation of cytochrome P450 2B10 (CYP2B10) expression in liver by peroxisome proliferator-activated receptor-\u03b2\/\u03b4 modulation of sp1 promoter occupancy. J. Biol. Chem.<\/i>, 291<\/b>, 25255\u201325263 (2016).","DOI":"10.1074\/jbc.M116.755447"},{"key":"136","doi-asserted-by":"crossref","unstructured":"136) Dunn W, Shah VH. Pathogenesis of alcoholic liver disease. Clin. Liver Dis.<\/i>, 20<\/b>, 445\u2013456 (2016).","DOI":"10.1016\/j.cld.2016.02.004"},{"key":"137","unstructured":"137) Osna NA, Donohue TM Jr, Kharbanda KK. Alcoholic liver disease: pathogenesis and current management. Alcohol Res.<\/i>, 38<\/b>, 147\u2013161 (2017)."},{"key":"138","doi-asserted-by":"crossref","unstructured":"138) Chu H, Jiang L, Gao B, Gautam N, Alamoudi JA, Lang S, Wang Y, Duan Y, Alnouti Y, Cable EE, Schnabl B. The selective PPAR-delta agonist seladelpar reduces ethanol-induced liver disease by restoring gut barrier function and bile acid homeostasis in mice. Transl. Res.<\/i>, 227<\/b>, 1\u201314 (2021).","DOI":"10.1016\/j.trsl.2020.06.006"},{"key":"139","doi-asserted-by":"crossref","unstructured":"139) Peters JM, Gonzalez FJ, M\u00fcller R. Establishing the Role of PPARbeta\/delta in carcinogenesis. Trends Endocrinol. Metab.<\/i>, 26<\/b>, 595\u2013607 (2015).","DOI":"10.1016\/j.tem.2015.09.004"},{"key":"140","doi-asserted-by":"crossref","unstructured":"140) Peters JM, Kim DJ, Bility MT, Borland MG, Zhu B, Gonzalez FJ. Regulatory mechanisms mediated by peroxisome proliferator-activated receptor-\u03b2\/\u03b4 in skin cancer. Mol. Carcinog.<\/i>, 58<\/b>, 1612\u20131622 (2019).","DOI":"10.1002\/mc.23033"},{"key":"141","doi-asserted-by":"crossref","unstructured":"141) Peters JM, Walter V, Patterson AD, Gonzalez FJ. Unraveling the role of peroxisome proliferator-activated receptor-\u03b2\/\u03b4 (PPAR\u03b2\/\u03b4) expression in colon carcinogenesis. NPJ Precis. Oncol.<\/i>, 3<\/b>, 26 (2019).","DOI":"10.1038\/s41698-019-0098-x"},{"key":"142","doi-asserted-by":"crossref","unstructured":"142) Blednov YA, Benavidez JM, Black M, Ferguson LB, Schoenhard GL, Goate AM, Edenberg HJ, Wetherill L, Hesselbrock V, Foroud T, Harris RA. Peroxisome proliferator-activated receptors \u03b1 and \u03b3 are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcohol. Clin. Exp. Res.<\/i>, 39<\/b>, 136\u2013145 (2015).","DOI":"10.1111\/acer.12610"},{"key":"143","doi-asserted-by":"crossref","unstructured":"143) Haile CN, Kosten TA. The peroxisome proliferator-activated receptor alpha agonist fenofibrate attenuates alcohol self-administration in rats. Neuropharmacology<\/i>, 116<\/b>, 364\u2013370 (2017).","DOI":"10.1016\/j.neuropharm.2017.01.007"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/44\/11\/44_b21-00486\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T03:55:32Z","timestamp":1636170932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/44\/11\/44_b21-00486\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":143,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b21-00486","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]},"article-number":"b21-00486"}}