{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:30:31Z","timestamp":1790037031920,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>We investigated whether short term high fructose intake may induce early hepatic dysfunction in rats and to test whether allopurinol treatment may have beneficial effects. Twenty male Sprague-Dawley rats received 20% fructose in drinking water (10 treated with allopurinol and 10 received vehicle) and 10 control rats received tap water. After 14 days, the hepatic response to an acute fructose load was evaluated, and in fasted animals, respirometry studies in freshly isolated mitochondria were performed. In fasting rats, we did not find differences in systemic or hepatic uric acid and triglyceride concentrations among the groups, but mitochondrial respiratory control rate was significantly decreased by high fructose feeding and correlated with a reduced expression of Complex I, as well as decreased aconitase-2 activity. On the other hand, in fructose fed rats, an acute fructose load increased systemic and hepatic uric acid, triglycerides and oxidative stress. Fructose feeding was also associated with fructokinase and xanthine oxidase overexpression and increased liver de novo lipogenesis program (fatty acid synthase (FAS) and cell death-inducing DFFA-like effector C (CIDEC) overexpression, ATP citrate lyase (ACL) and acetyl coA carboxylase (ACC) overactivity and decreased AMP-activated protein kinase (AMPk) and endothelial nitric oxide synthase (eNOS) activation). Allopurinol treatment prevented hepatic and systemic alterations. These data suggest that early treatment with xanthine oxidase inhibitors might provide a therapeutic advantage by delaying or even halting the progression of non-alcoholic fatty liver disease (NAFLD).<\/jats:p>","DOI":"10.3390\/biom9100601","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T10:53:03Z","timestamp":1570791183000},"page":"601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Allopurinol Prevents the Lipogenic Response Induced by an Acute Oral Fructose Challenge in Short-Term Fructose Fed Rats"],"prefix":"10.3390","volume":"9","author":[{"given":"Fernando E.","family":"Garc\u00eda-Arroyo","sequence":"first","affiliation":[{"name":"Department of Cardio-Renal Physiopathology, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Monroy-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Physiopathology, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzel","family":"Mu\u00f1oz-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Physiopathology, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Gonzaga","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Physiopathology, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Andr\u00e9s-Hernando","sequence":"additional","affiliation":[{"name":"Renal Diseases and Hypertension University of Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1068-316X","authenticated-orcid":false,"given":"Cecilia","family":"Zazueta","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biomedicine, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8864-2304","authenticated-orcid":false,"given":"J. Gabriel","family":"Ju\u00e1rez-Rojas","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Lanaspa","sequence":"additional","affiliation":[{"name":"Renal Diseases and Hypertension University of Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Renal Diseases and Hypertension University of Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-9617","authenticated-orcid":false,"given":"L. Gabriela","family":"S\u00e1nchez-Lozada","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Physiopathology, INC Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/ajcn\/86.4.899","article-title":"Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease","volume":"86","author":"Johnson","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1096\/fasebj.4.9.2189777","article-title":"Metabolic effects of dietary fructose","volume":"4","author":"Hallfrisch","year":"1990","journal-title":"FASEB J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/07315724.1986.10720113","article-title":"Plasma fructose, uric acid, and inorganic phosphorus responses of hyperinsulinemic men fed fructose","volume":"5","author":"Hallfrisch","year":"1986","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.clnu.2015.04.001","article-title":"Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A (31)P MRS study","volume":"35","author":"Bawden","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/682673","article-title":"Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension","volume":"2013","author":"Khitan","year":"2013","journal-title":"J. Nutr. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.metabol.2011.01.008","article-title":"Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake","volume":"60","author":"Lanaspa","year":"2011","journal-title":"Metabolism"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1001\/jama.282.17.1659","article-title":"Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: A pilot study","volume":"282","author":"Chatham","year":"1999","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"F625","DOI":"10.1152\/ajprenal.00140.2005","article-title":"A causal role for uric acid in fructose-induced metabolic syndrome","volume":"290","author":"Nakagawa","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"F710","DOI":"10.1152\/ajprenal.00454.2007","article-title":"Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome","volume":"294","author":"Tapia","year":"2008","journal-title":"AJP Ren. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/ijo.2009.259","article-title":"Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response","volume":"34","author":"Schold","year":"2010","journal-title":"Int. J. Obes. (Lond)"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"40732","DOI":"10.1074\/jbc.M112.399899","article-title":"Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver","volume":"287","author":"Lanaspa","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lanaspa, M.A., Sanchez-Lozada, L.G., Cicerchi, C., Li, N., Roncal-Jimenez, C.A., Ishimoto, T., Le, M., Garcia, G.E., Thomas, J.B., and Rivard, C.J. (2012). Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047948"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.jhep.2015.11.022","article-title":"Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3 inflammasome-dependent mechanism","volume":"64","author":"Wan","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4272","DOI":"10.1074\/jbc.RA118.006158","article-title":"Uric acid activates aldose reductase and the polyol pathway for endogenous fructose and fat production causing development of fatty liver in rats","volume":"294","author":"Cicerchi","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_15","first-page":"98","article-title":"Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss","volume":"26","author":"Luyckx","year":"2000","journal-title":"Diabetes Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrgastro.2010.41","article-title":"The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome","volume":"7","author":"Lim","year":"2010","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.jhep.2016.05.005","article-title":"A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer","volume":"65","author":"Asgharpour","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/oby.22472","article-title":"Are Liquid Sugars Different from Solid Sugar in Their Ability to Cause Metabolic Syndrome?","volume":"27","author":"Sundborn","year":"2019","journal-title":"Obesity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.molmet.2019.05.010","article-title":"Impact of dietary sucrose on adiposity and glucose homeostasis in C57BL\/6J mice depends on mode of ingestion: liquid or solid","volume":"27","author":"Togo","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gordish, K.L., Kassem, K.M., Ortiz, P.A., and Beierwaltes, W.H. (2017). Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide. Physiol. Rep., 5.","DOI":"10.14814\/phy2.13162"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0003-9861(85)90235-8","article-title":"Evidence for the involvement of dithiol groups in mitochondrial calcium transport: studies with cadmium","volume":"242","author":"Chavez","year":"1985","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10863-008-9186-2","article-title":"Relationship between oxidative stress and mitochondrial function in the post-conditioned heart","volume":"40","author":"Correa","year":"2008","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29405","DOI":"10.1016\/S0021-9258(18)43893-8","article-title":"Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not","volume":"269","author":"Hausladen","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1038\/ijo.2016.10","article-title":"Added sugars and risk factors for obesity, diabetes and heart disease","volume":"40","author":"Rippe","year":"2016","journal-title":"Int. J. Obes. (London)"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/hep.25741","article-title":"Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes","volume":"56","author":"Abdelmalek","year":"2012","journal-title":"Hepatology"},{"key":"ref_26","first-page":"G71","article-title":"Rapid reversible substrate regulation of fructose transporter expression in rat small intestine and kidney","volume":"267","author":"Burant","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1042\/bj2950211","article-title":"Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars","volume":"295","author":"Miyamoto","year":"1993","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/ijpo.238","article-title":"Oral fructose absorption in obese children with non-alcoholic fatty liver disease","volume":"10","author":"Sullivan","year":"2015","journal-title":"Pediatr. Obes."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.jash.2015.07.008","article-title":"A pilot study on the impact of a low fructose diet and allopurinol on clinic blood pressure among overweight and prehypertensive subjects: a randomized placebo controlled trial","volume":"9","author":"Madero","year":"2015","journal-title":"J. Am. Soc. Hypertens."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2018.01.019","article-title":"Fructose and sugar: A major mediator of non-alcoholic fatty liver disease","volume":"68","author":"Jensen","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/j.jhep.2015.01.019","article-title":"Xanthine oxidase in non-alcoholic fatty liver disease and hyperuricemia: One stone hits two birds","volume":"62","author":"Xu","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/labinvest.2014.98","article-title":"Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes","volume":"94","author":"Choi","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.fct.2017.02.039","article-title":"Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL\/6J female mice: Role of disturbed lipid homeostasis and increased oxidative stress","volume":"103","author":"Choi","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2008.08.068","article-title":"Oxidative stress induced lipid accumulation via SREBP1c activation in HepG2 cells","volume":"375","author":"Sekiya","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1248\/bpb.33.346","article-title":"A physiological role for fat specific protein 27\/cell death-inducing DFF45-like effector C in adipose and liver","volume":"33","author":"Matsusue","year":"2010","journal-title":"Biol. Pharm. Bull"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.cmet.2008.03.003","article-title":"Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27","volume":"7","author":"Matsusue","year":"2008","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E1395","DOI":"10.1152\/ajpendo.00188.2009","article-title":"Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA","volume":"297","author":"Liu","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"G540","DOI":"10.1152\/ajpgi.00247.2014","article-title":"Chronic NOS inhibition accelerates NAFLD progression in an obese rat model","volume":"308","author":"Sheldon","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1053\/j.gastro.2004.09.049","article-title":"The role of AMP-activated protein kinase in the action of ethanol in the liver","volume":"127","author":"You","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1016\/j.bbagen.2015.09.008","article-title":"Cidec promotes the differentiation of human adipocytes by degradation of AMPKalpha through ubiquitin-proteasome pathway","volume":"1850","author":"Xu","year":"2015","journal-title":"BBA General Subj."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/10\/601\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:25:23Z","timestamp":1760189123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/10\/601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,11]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["biom9100601"],"URL":"https:\/\/doi.org\/10.3390\/biom9100601","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,11]]}}}