{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:06:14Z","timestamp":1791194774488,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T00:00:00Z","timestamp":1328832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Pentoxifylline is in clinical trials for non\u2010alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Pentoxifylline (100\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) was administered for 4 days or 3 weeks in lean and obese\/diabetic <jats:italic>ob\/ob<\/jats:italic> mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids <jats:italic>in vivo<\/jats:italic> were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT\u2010PCR and Western blotting.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Four days of pentoxifylline treatment slightly increased liver lipids in <jats:italic>ob\/ob<\/jats:italic> mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in <jats:italic>ob\/ob<\/jats:italic> mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, <jats:italic>ob\/ob<\/jats:italic> mice treated with pentoxifylline. During the first 10\u2003min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline\u2010treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline\u2010treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in <jats:italic>ob\/ob<\/jats:italic>, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline\u2010treated <jats:italic>ob\/ob<\/jats:italic> mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in <jats:italic>ob\/ob<\/jats:italic> liver.<\/jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS<\/jats:bold> Pentoxifylline exacerbated fatty liver in <jats:italic>ob\/ob<\/jats:italic> mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long\u2010term treatment with pentoxifylline could worsen fatty liver in some patients with pre\u2010existing hyperglycaemia.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01580.x","type":"journal-article","created":{"date-parts":[[2011,7,14]],"date-time":"2011-07-14T10:07:33Z","timestamp":1310638053000},"page":"1361-1374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pentoxifylline aggravates fatty liver in obese and diabetic <i>ob\/ob<\/i> mice by increasing intestinal glucose absorption and activating hepatic lipogenesis"],"prefix":"10.1111","volume":"165","author":[{"given":"J","family":"Massart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MA","family":"Robin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Noury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Fautrel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Lett\u00e9ron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Bado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PA","family":"Eliat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Fromenty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.40064.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90617.2008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.4.1233"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1985.6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2005.10.004"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00379.2007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.337"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmec.2009.02.002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0399-8320(04)95062-2"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb32915.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.608"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00332.2001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.022491"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21536"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.32"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e3282ff5e55"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2008.05.006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1327"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25256"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.03.008"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23280"},{"issue":"1","key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1002\/hep.20973","article-title":"Nonalcoholic fatty liver disease: from steatosis to cirrhosis","volume":"43","author":"Farrell GC","year":"2006","journal-title":"Hepatology"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(94)90026-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.155168"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00568.2003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0780-x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1177\/135965350701200314","article-title":"High doses of stavudine induce fat wasting and mild liver damage without impairing mitochondrial respiration in mice","volume":"12","author":"Igoudjil A","year":"2007","journal-title":"Antivir Ther"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405238101"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111041200"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.28.061807.155518"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0104318"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.06.030"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.01.040"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-008-9058-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158042"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50309"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2007.117"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22064"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2009.02.005"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.10121"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(07)70044-7"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9574LSF"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00500824"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800042-JLR200"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20949"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04756.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000282097"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6989(83)80055-1"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1994.sp003753"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2010.07.003"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13209"},{"key":"e_1_2_8_54_1","first-page":"3","article-title":"Modulation of inflammatory response by pentoxifylline is independent of heme oxygenase\u20101 pathway","volume":"60","author":"Taha H","year":"2009","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.06.008"},{"key":"e_1_2_8_56_1","first-page":"28","article-title":"The impact of prandial glucose regulation in practice","volume":"15","author":"Verg\u00e8s B","year":"2002","journal-title":"Diabetes Nutr Metab"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(96)00314-X"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6918(03)00107-0"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.2307\/3580209"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2011.01580.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2011.01580.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T11:37:04Z","timestamp":1697456224000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01580.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,10]]},"references-count":58,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1111\/j.1476-5381.2011.01580.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01580.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,10]]},"assertion":[{"value":"2012-02-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}