{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:11:50Z","timestamp":1791904310181,"version":"4.3.4"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1095,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP depletion after an intravenous (IV) fructose challenge test in low- versus high-fructose consumers was assessed. We evaluated diabetic adults enrolled in the Action for Health in Diabetes Fatty Liver Ancillary Study (n = 244) for whom dietary fructose consumption estimated by a 130-item food frequency questionnaire and hepatic ATP measured by phosphorus magnetic resonance spectroscopy and uric acid (UA) levels were performed (n = 105). In a subset of participants (n = 25), an IV fructose challenge was utilized to assess change in hepatic ATP content. The relationships between dietary fructose, UA, and hepatic ATP depletion at baseline and after IV fructose challenge were evaluated in low- (&lt;15 g\/day) versus high-fructose (\u226515 g\/day) consumers. High dietary fructose consumers had slightly lower baseline hepatic ATP levels and a greater absolute change in hepatic \u03b1-ATP\/ inorganic phosphate (Pi) ratio (0.08 versus 0.03;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.05) and \u03b3-ATP \/Pi ratio after an IV fructose challenge (0.03 versus 0.06;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.06). Patients with high UA (\u22655.5 mg\/dL) showed a lower minimum liver ATP\/Pi ratio postfructose challenge (4.5 versus 7.0;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.04).<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusions:\n                                 <\/jats:bold>\n                                 <jats:bold>High-fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion after an IV fructose challenge. Subjects with high UA show a greater nadir in hepatic ATP in response to fructose. Both high dietary fructose intake and elevated UA level may predict more severe hepatic ATP depletion in response to fructose and hence may be risk factors for the development and progression of NAFLD.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.25741","type":"journal-article","created":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T07:20:07Z","timestamp":1333264807000},"page":"952-960","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":171,"title":["Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes"],"prefix":"10.1097","volume":"56","author":[{"given":"Manal F.","family":"Abdelmalek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Lazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Horska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Bonekamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Lipkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Balasubramanyam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Bantle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Mae","family":"Diehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne M.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-19-20250207","doi-asserted-by":"crossref","first-page":"S99S112","DOI":"10.1002\/hep.20973","article-title":"Nonalcoholic fatty liver disease: from steatosis to cirrhosis.","volume":"43","author":"Farrell","year":"2006","journal-title":"HEPATOLOGY"},{"key":"R2-19-20250207","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/ajcn\/79.4.537","article-title":"Consumption of highfructose corn syrup in beverages may play a role in the epidemic of obesity.","volume":"79","author":"Bray","year":"2004","journal-title":"Am J Clin 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Hepatol"},{"key":"R7-19-20250207","doi-asserted-by":"crossref","first-page":"F625F631","DOI":"10.1152\/ajprenal.00140.2005","article-title":"A causal role for uric acid in fructoseinduced metabolic syndrome.","volume":"290","author":"Nakagawa","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"key":"R8-19-20250207","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":"PerezPozo","year":"2010","journal-title":"Int J Obes (Lond)"},{"key":"R9-19-20250207","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-009-0042-x","article-title":"Comparison of free fructose and glucose to sucrose in the ability to cause fatty liver.","volume":"49","author":"SanchezLozada","year":"2010","journal-title":"Eur J 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A kinetic study of liver adenylate deaminase.","volume":"162","author":"van den Berghe","year":"1977","journal-title":"Biochem J"},{"key":"R16-19-20250207","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1681\/ASN.2008060576","article-title":"Ketohexokinasedependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells.","volume":"20","author":"Cirillo","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"R17-19-20250207","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1681\/ASN.2007121304","article-title":"Fructose induces the inflammatory molecule ICAM1 in endothelial cells.","volume":"19","author":"Glushakova","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"R18-19-20250207","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":"CortezPinto","year":"1999","journal-title":"JAMA"},{"key":"R19-19-20250207","first-page":"466","article-title":"Hepatic ATP reserve and efficiency of replenishing: comparison between obese and nonobese normal individuals.","volume":"98","author":"Nair","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"R20-19-20250207","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/j.1365-2362.1973.tb02211.x","article-title":"Depletion of liver adenosine phosphates and metabolic effects of intravenous infusion of fructose or sorbitol in man and in the rat.","volume":"3","author":"Bode","year":"1973","journal-title":"Eur J Clin Invest"},{"key":"R21-19-20250207","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/jn\/138.6.1039","article-title":"Dietary sugars stimulate fatty acid synthesis in adults.","volume":"138","author":"Parks","year":"2008","journal-title":"J Nutr"},{"key":"R22-19-20250207","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/hep.510290428","article-title":"Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver.","volume":"29","author":"Rashid","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R23-19-20250207","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1074\/jbc.275.12.9047","article-title":"The cJun NH(2)terminal kinase promotes insulin resistance during association with insulin receptor substrate1 and phosphorylation of Ser(307).","volume":"275","author":"Aguirre","year":"2000","journal-title":"J Biol Chem"},{"key":"R24-19-20250207","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1074\/jbc.274.9.5692","article-title":"Obesity induces expression of uncoupling protein2 in hepatocytes and promotes liver ATP depletion.","volume":"274","author":"Chavin","year":"1999","journal-title":"J Biol Chem"},{"key":"R25-19-20250207","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1210\/er.2008-0033","article-title":"Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes?","volume":"30","author":"Johnson","year":"2009","journal-title":"Endocr Rev"},{"key":"R26-19-20250207","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/S0140-6736(70)92269-5","article-title":"Fructoseinduced hyperuricaemia.","volume":"2","author":"Stirpe","year":"1970","journal-title":"Lancet"},{"key":"R27-19-20250207","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jhep.2008.11.021","article-title":"Association of serum uric acid level with nonalcoholic fatty liver disease: a crosssectional study.","volume":"50","author":"Li","year":"2009","journal-title":"J Hepatol"},{"key":"R28-19-20250207","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1365-2036.2011.04788.x","article-title":"Hyperuricemia is associated with histological liver damage in patients with nonalcoholic fatty liver disease.","volume":"34","author":"Petta","year":"2011","journal-title":"Aliment Pharmacol Ther"},{"key":"R29-19-20250207","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/hep.23717","article-title":"Association between serum uric acid level and chronic liver disease in the United States.","volume":"52","author":"Afzali","year":"2010","journal-title":"HEPATOLOGY"},{"key":"R30-19-20250207","first-page":"455","article-title":"Dietary regulation of fructose metabolism in the intestine and in the liver of the rat. 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The Lifetime Drinking History and the MAST.","volume":"43","author":"Skinner","year":"1982","journal-title":"J Stud Alcohol"},{"key":"R33-19-20250207","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.jada.2009.05.016","article-title":"Action for Health in Diabetes (Look AHEAD) trial: baseline evaluation of selected nutrients and food group intake.","volume":"109","author":"Vitolins","year":"2009","journal-title":"J Am Diet Assoc"},{"key":"R34-19-20250207","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1478-3231.2008.01705.x","article-title":"Hepatic fat and adenosine triphosphate measurement in overweight and obese adults using 1H and 31P magnetic resonance spectroscopy.","volume":"28","author":"Solga","year":"2008","journal-title":"Liver Int"},{"key":"R35-19-20250207","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jmr.2005.11.004","article-title":"Quantifying in vivo MR spectra with circles.","volume":"179","author":"Gabr","year":"2006","journal-title":"J Magn Reson"},{"key":"R36-19-20250207","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/mrm.21762","article-title":"Threedimensional highresolution magnetic resonance spectroscopic imaging for absolute quantification of 31P metabolites in human liver.","volume":"60","author":"Chmelik","year":"2008","journal-title":"Magn Reson Med"},{"key":"R37-19-20250207","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/nbm.1940040606","article-title":"Is cellular integrity responsible for the partial NMR invisibility of ATP in isolated ischemic rat liver?","volume":"4","author":"Gallis","year":"1991","journal-title":"NMR Biomed"},{"key":"R38-19-20250207","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1148\/radiology.173.2.2798871","article-title":"Alcoholic liver disease: quantitative imageguided P31 MR spectroscopy.","volume":"173","author":"Meyerhoff","year":"1989","journal-title":"Radiology"},{"key":"R39-19-20250207","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/jmri.1880020211","article-title":"Quantitative P31 MR spectroscopy of the liver in alcoholic cirrhosis.","volume":"2","author":"Rajanayagam","year":"1992","journal-title":"J Magn Reson Imaging"},{"key":"R40-19-20250207","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/hep.23093","article-title":"Abnormal hepatic energy homeostasis in type 2 diabetes.","volume":"50","author":"Szendroedi","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R41-19-20250207","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1002\/hep.22851","article-title":"Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis.","volume":"49","author":"Caldwell","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R42-19-20250207","first-page":"1","article-title":"Fructose: metabolism and shortterm effects on carbohydrate and purine metabolic pathways.","volume":"21","author":"Van den Berghe","year":"1986","journal-title":"Prog Biochem Pharmacol"},{"key":"R43-19-20250207","first-page":"373","article-title":"Hyperuricemia induced by fructose load in liver cirrhosis.","volume":"24","author":"Budillon","year":"1992","journal-title":"Ital J Gastroenterol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.25741","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201209000-00019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T16:50:34Z","timestamp":1738947034000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201209000-00019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.25741","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2012,9]]}}}