{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:20:25Z","timestamp":1790659225387,"version":"4.1.0"},"reference-count":105,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"THE PUBLIC FOUNDATION OF ELIZABETH ARNOLD- FUJI","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"THE PUBLIC FOUNDATION OF ELIZABETH ARNOLD- FUJI","award":["2022\u20132024"],"award-info":[{"award-number":["2022\u20132024"]}]},{"name":"THE PUBLIC FOUNDATION OF ELIZABETH ARNOLD- FUJI","award":["20K11645."],"award-info":[{"award-number":["20K11645."]}]},{"name":"The Japan Diabetes Society Carrier Development Award supported by Sanofi","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"The Japan Diabetes Society Carrier Development Award supported by Sanofi","award":["2022\u20132024"],"award-info":[{"award-number":["2022\u20132024"]}]},{"name":"The Japan Diabetes Society Carrier Development Award supported by Sanofi","award":["20K11645."],"award-info":[{"award-number":["20K11645."]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["2022\u20132024"],"award-info":[{"award-number":["2022\u20132024"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K11645."],"award-info":[{"award-number":["20K11645."]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Excess fructose intake is associated with obesity, fatty liver, tooth decay, cancer, and cardiovascular diseases. Even after the ingestion of fructose, fructose concentration in the portal blood is never high; fructose is further metabolized in the liver, and the blood fructose concentration is 1\/100th of the glucose concentration. It was previously thought that fructose was metabolized in the liver and not in the small intestine, but it has been reported that metabolism in the small intestine also plays an important role in fructose metabolism. Glut5 knockout mice exhibit poor fructose absorption. In addition, endogenous fructose production via the polyol pathway has also received attention; gene deletion of aldose reductase (Ar), ketohexokinase (Khk), and triokinase (Tkfc) has been found to prevent the development of fructose-induced liver lipidosis. Carbohydrate response element-binding protein (Chrebp) regulates the expression of Glut5, Khk, aldolase b, and Tkfc. We review fructose metabolism with a focus on the roles of the glucose-activating transcription factor Chrebp, fructolysis, and the polyol pathway.<\/jats:p>","DOI":"10.3390\/nu15071778","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T01:10:27Z","timestamp":1680743427000},"page":"1778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Recent Progress on Fructose Metabolism\u2014Chrebp, Fructolysis, and Polyol Pathway"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-6238","authenticated-orcid":false,"given":"Katsumi","family":"Iizuka","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition, Fujita Health University, Toyoake 470-1192, Japan"},{"name":"Food and Nutrition Service Department, Fujita Health University Hospital, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"ref_1","unstructured":"(2023, February 05). WHO Guidelines. Available online: https:\/\/www.who.int\/news\/item\/04-03-2015-who-calls-on-countries-to-reduce-sugars-intake-among-adults-and-children."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dietary Guidelines Advisory Committee (2020). Scientific Report of the 2020 Dietary Guidelines Advisory Committee: Advisory Report to the Secretary of Agriculture and the Secretary of Health and Human Services. US Department of Agriculture.","DOI":"10.52570\/DGAC2020"},{"key":"ref_3","first-page":"727","article-title":"Association of all-cause mortality with sugar intake from different sources in the prospective cohort of UK Biobank participants","volume":"62","author":"Kaiser","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-nutr-062220-025831","article-title":"Dietary Fructose and Fructose-Induced Pathologies","volume":"42","author":"Jung","year":"2022","journal-title":"Annu. Rev. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1111\/jdi.13305","article-title":"Does the breakdown of the detoxification system for aldehydes as a result of aldose reductase upregulation lead to alcohol-induced liver injury in humans and mice?","volume":"11","author":"Hotta","year":"2020","journal-title":"J. Diabetes Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1146\/annurev-biochem-070820-125228","article-title":"Short- and Long-Term Adaptation to Altered Levels of Glucose: Fifty Years of Scientific Adventure","volume":"90","author":"Uyeda","year":"2021","journal-title":"Annu. Rev. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Iizuka, K. (2021). The Roles of Carbohydrate Response Element Binding Protein in the Relationship between Carbohydrate Intake and Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222112058"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100346","DOI":"10.1016\/j.jhepr.2021.100346","article-title":"New targets for NAFLD","volume":"3","author":"Parlati","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/j.cmet.2021.09.010","article-title":"Molecular aspects of fructose metabolism and metabolic disease","volume":"33","author":"Herman","year":"2021","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Iizuka, K. (2017). The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism. Nutrients, 9.","DOI":"10.3390\/nu9020181"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"429","DOI":"10.5483\/BMBRep.2018.51.9.197","article-title":"Recent insights into the role of ChREBP in intestinal fructose absorption and metabolism","volume":"51","author":"Lee","year":"2018","journal-title":"BMB Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/joim.12993","article-title":"Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts","volume":"287","author":"Johnson","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.3390\/nu6083117","article-title":"Normal roles for dietary fructose in carbohydrate metabolism","volume":"6","author":"Laughlin","year":"2014","journal-title":"Nutrients"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"G779","DOI":"10.1152\/ajpgi.00188.2015","article-title":"Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK\u2212\/\u2212 and GLUT5\u2212\/\u2212 mice","volume":"309","author":"Patel","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.cmet.2017.12.016","article-title":"The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids","volume":"27","author":"Jang","year":"2018","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1432-1033.1969.tb00696.x","article-title":"Enzymes involved in fructose metabolism in liver and the glyceraldehyde metabolic crossroads","volume":"10","author":"Sillero","year":"1969","journal-title":"Eur. J. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kato, T., Iizuka, K., Takao, K., Horikawa, Y., Kitamura, T., and Takeda, J. (2018). ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption. Nutrients, 10.","DOI":"10.20944\/preprints201802.0005.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e96703","DOI":"10.1172\/jci.insight.96703","article-title":"Intestinal, but not hepatic, ChREBP is required for fructose tolerance","volume":"2","author":"Kim","year":"2017","journal-title":"JCI Insight"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.metabol.2018.04.006","article-title":"ChREBP deficiency leads to diarrhea-predominant irritable bowel syndrome","volume":"85","author":"Oh","year":"2018","journal-title":"Metabolism"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1172\/JCI102569","article-title":"Metabolism of intravenous fructose and glucose in normal and diabetic subjects","volume":"31","author":"Miller","year":"1952","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bbrc.2009.09.109","article-title":"Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus","volume":"390","author":"Koo","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1210\/jc.2013-3856","article-title":"Spinas, Kaspar Berneis, Sugar-Sweetened Beverages With Moderate Amounts of Fructose, but Not Sucrose, Induce Fatty Acid Synthesis in Healthy Young Men: A Randomized Crossover Study","volume":"99","author":"Hochuli","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jhep.2021.02.027","article-title":"Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial","volume":"75","author":"Hochuli","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7281","DOI":"10.1073\/pnas.0401516101","article-title":"Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis","volume":"101","author":"Iizuka","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28721","DOI":"10.1074\/jbc.M601576200","article-title":"ChREBP*Mlx is the principal mediator of glucose-induced gene expression in the liver","volume":"281","author":"Ma","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9116","DOI":"10.1073\/pnas.161284298","article-title":"A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver","volume":"98","author":"Yamashita","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"32746","DOI":"10.1074\/jbc.M201635200","article-title":"ChREBP rather than USF2 regulates glucose stimulation of endogenous L-pyruvate kinase expression in insulin-secreting cells","volume":"277","author":"Wang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1194\/jlr.M600289-JLR200","article-title":"ChREBP binding to fatty acid synthase and L-type pyruvate kinase genes is stimulated by glucose in pancreatic beta-cells","volume":"47","author":"Rutter","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.2337\/db15-0239","article-title":"Induction of the ChREBP\u03b2 Isoform Is Essential for Glucose-Stimulated \u03b2-Cell Proliferation","volume":"64","author":"Zhang","year":"2015","journal-title":"Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature10986","article-title":"A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism","volume":"484","author":"Herman","year":"2012","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/s41366-022-01082-7","article-title":"ChREBP-regulated lipogenesis is not required for the thermogenesis of brown adipose tissue","volume":"46","author":"Wei","year":"2022","journal-title":"Int. J. Obes."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cmet.2017.10.008","article-title":"Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis","volume":"27","author":"Tang","year":"2018","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1530\/JOE-20-0442","article-title":"Effects of ChREBP deficiency on adrenal lipogenesis and steroidogenesis","volume":"248","author":"Takao","year":"2021","journal-title":"J. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1507\/endocrj.EJ13-0079","article-title":"Feedback looping between ChREBP and PPAR\u03b1 in the regulation of lipid metabolism in brown adipose tissues","volume":"60","author":"Iizuka","year":"2013","journal-title":"Endocr. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108050","DOI":"10.1016\/j.jdiacomp.2021.108050","article-title":"ChREBP deficiency alleviates apoptosis by inhibiting TXNIP\/oxidative stress in diabetic nephropathy","volume":"35","author":"Chen","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.molmet.2016.09.010","article-title":"Islet ChREBP-\u03b2 is increased in diabetes and controls ChREBP-\u03b1 and glucose-induced gene expression via a negative feedback loop","volume":"5","author":"Jing","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e153431","DOI":"10.1172\/jci.insight.153431","article-title":"ChREBP\u03b2 is dispensable for the control of glucose homeostasis and energy balance","volume":"7","author":"Recazens","year":"2022","journal-title":"JCI Insight"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.tem.2013.01.003","article-title":"Novel insights into ChREBP regulation and function","volume":"24","author":"Filhoulaud","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1074\/jbc.M115.708982","article-title":"Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): Role of AMP as an allosteric inhibitor","volume":"291","author":"Sato","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1074\/jbc.M107895200","article-title":"Mechanism for fatty acid \u201csparing\u201d effect on glucose-induced transcription: Regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase","volume":"277","author":"Kawaguchi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13710","DOI":"10.1073\/pnas.231370798","article-title":"Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation\/dephosphorylation of the carbohydrate response element binding protein","volume":"98","author":"Kawaguchi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1073\/pnas.0730817100","article-title":"Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver","volume":"100","author":"Kabashima","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.bbrc.2010.04.028","article-title":"Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)","volume":"395","author":"Li","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jhep.2011.07.019","article-title":"Glucose 6-phosphate, rather than xylulose 5-phosphate, is required for the activation of ChREBP in response to glucose in the liver","volume":"56","author":"Dentin","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1507\/endocrj.EJ12-0413","article-title":"Role of glucose-6-phosphate and xylulose-5-phosphate in the regulation of glucose-stimulated gene expression in the pancreatic \u03b2 cell line, INS-1E","volume":"60","author":"Iizuka","year":"2013","journal-title":"Endocr. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26341","DOI":"10.1074\/jbc.270.44.26341","article-title":"Purification and characterization of a novel xylulose 5-phosphate-activated protein phosphatase catalyzing dephosphorylation of fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase","volume":"270","author":"Nishimura","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8394","DOI":"10.1016\/S0021-9258(19)68856-3","article-title":"The effect of natural and synthetic D-fructose 2,6-bisphosphate on the regulatory kinetic properties of liver and muscle phosphofructokinases","volume":"256","author":"Uyeda","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cmet.2020.07.018","article-title":"Triose Kinase Controls the Lipogenic Potential of Fructose and Dietary Tolerance","volume":"32","author":"Liu","year":"2020","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"McFerrin, L.G., and Atchley, W.R. (2012). A novel N-terminal domain may dictate the glucose response of Mondo proteins. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034803"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1042\/BJ20111280","article-title":"Fructose 2,6-bisphosphate is essential for glucose-regulated gene transcription of glucose-6-phosphatase and other ChREBP target genes in hepatocytes","volume":"443","author":"Arden","year":"2012","journal-title":"Biochem. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E358","DOI":"10.1152\/ajpendo.00027.2006","article-title":"Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob\/ob) mice","volume":"291","author":"Iizuka","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.2337\/db06-0200","article-title":"Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob\/ob mice","volume":"55","author":"Dentin","year":"2006","journal-title":"Diabetes"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1194\/jlr.M081836","article-title":"Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice","volume":"59","author":"Linden","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"591","DOI":"10.2337\/db19-0388","article-title":"Liver ChREBP Protects Against Fructose-Induced Glycogenic Hepatotoxicity by Regulating L-Type Pyruvate Kinase","volume":"69","author":"Shi","year":"2020","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E788","DOI":"10.1152\/ajpendo.00510.2006","article-title":"The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions","volume":"292","author":"Pedersen","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1042\/BJ20101225","article-title":"Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor \u03b1 (LXR\u03b1) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1","volume":"432","author":"Grefhorst","year":"2010","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1002\/hep.31198","article-title":"Hepatic Carbohydrate Response Element Binding Protein Activation Limits Nonalcoholic Fatty Liver Disease Development in a Mouse Model for Glycogen Storage Disease Type 1a","volume":"72","author":"Lei","year":"2020","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101108","DOI":"10.1016\/j.molmet.2020.101108","article-title":"The absence of hepatic glucose-6 phosphatase\/ChREBP couple is incompatible with survival in mice","volume":"43","author":"Rajas","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10024-001-0139-6","article-title":"Histologic features of the liver in type Ia glycogen storage disease: Comparative study between different age groups and consecutive biopsies","volume":"5","author":"Ciliv","year":"2002","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1172\/JCI89934","article-title":"Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity","volume":"127","author":"Zhang","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3164\/jcbn.09-93","article-title":"Eucalyptus leaf extract suppresses the postprandial elevation of portal, cardiac, and peripheral fructose concentrations after sucrose ingestion in rats","volume":"46","author":"Sugimoto","year":"2012","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1681\/ASN.2019101015","article-title":"Fructose Production and Metabolism in the Kidney","volume":"31","author":"Nakagawa","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1093\/oxfordjournals.humrep.a019138","article-title":"Effects of sperm activity on zinc and fructose concentrations in seminal plasma","volume":"11","author":"Aird","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/014850102753385170","article-title":"Fructose concentrations in seminal plasma from men with nonobstructive azoospermia","volume":"48","author":"Buckett","year":"2002","journal-title":"Arch. Androl."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1042\/bj3120757","article-title":"Sugar-dependent expression of the fructose transporter GLUT5 in Caco-2 cells","volume":"312","author":"Mesonero","year":"1995","journal-title":"Biochem. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1042\/bj3010169","article-title":"Regulation of expression of the human fructose transporter (GLUT5) by cyclic AMP","volume":"301","author":"Mahraoui","year":"1994","journal-title":"Biochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1042\/bj20030661","article-title":"Fructose modulates GLUT5 mRNA stability in differentiated Caco-2 cells: Role of cAMP-signaling pathway and PABP (polyadenylated-binding protein)-interacting protein (Paip) 2","volume":"375","author":"Gouyon","year":"2003","journal-title":"Biochem. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1042\/bj3390233","article-title":"Glucose and thyroid hormone coregulate the expression of the intestinal fructose transporter GLUT5","volume":"339","author":"Mesonero","year":"1999","journal-title":"Biochem J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9299","DOI":"10.1038\/s41598-019-45803-x","article-title":"Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR","volume":"9","author":"Zwarts","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Taneva, I., Grumann, D., Schmidt, D., Taneva, E., von Arnim, U., Ansorge, T., and Wex, T. (2022). Gene variants of the SLC2A5 gene encoding GLUT5, the major fructose transporter, do not contribute to clinical presentation of acquired fructose malabsorption. BMC Gastroenterol., 22.","DOI":"10.1186\/s12876-022-02244-7"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1074\/jbc.M808128200","article-title":"Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension","volume":"284","author":"Barone","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100217","DOI":"10.1016\/j.jhepr.2020.100217","article-title":"Ketohexokinase inhibition improves NASH by reducing fructose-induced steatosis and fibrogenesis","volume":"3","author":"Shepherd","year":"2020","journal-title":"JHEP Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1093\/hmg\/3.9.1627","article-title":"Molecular basis of essential fructosuria: Molecular cloning and mutational analysis of human ketohexokinase (fructokinase)","volume":"3","author":"Bonthron","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Tran, C. (2017). Inborn Errors of Fructose Metabolism. What Can We Learn from Them?. Nutrients, 9.","DOI":"10.3390\/nu9040356"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/adc.36.187.273","article-title":"Essential benign fructosuria","volume":"36","author":"Laron","year":"1961","journal-title":"Arch. Dis. Child."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1203\/00006450-199410000-00004","article-title":"Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy","volume":"36","author":"Boesiger","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1172\/JCI94427","article-title":"Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice","volume":"128","author":"Lanaspa","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3945\/an.116.013912","article-title":"Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases","volume":"8","author":"Gugliucci","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ymgme.2015.01.001","article-title":"Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans","volume":"114","author":"Oppelt","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1002\/hep.32064","article-title":"Fructose-1,6-Bisphosphate Aldolase B Depletion Promotes Hepatocellular Carcinogenesis Through Activating Insulin Receptor Signaling and Lipogenesis","volume":"74","author":"Liu","year":"2021","journal-title":"Hepatology"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"He, X., Li, M., Yu, H., Liu, G., Wang, N., Yin, C., Tu, Q., Narla, G., Tao, Y., and Cheng, S. (2020). Loss of hepatic aldolase B activates Akt and promotes hepatocellular carcinogenesis by destabilizing the Aldob\/Akt\/PP2A protein complex. PLoS Biol., 18.","DOI":"10.1101\/2020.06.09.141986"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10620","DOI":"10.1074\/jbc.M113.525626","article-title":"Bifunctional homodimeric triokinase\/FMN cyclase: Contribution of protein domains to the activities of the human enzyme and molecular dynamics simulation of domain movements","volume":"289","author":"Rodrigues","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ajhg.2020.01.005","article-title":"Biallelic Variants in TKFC Encoding Triokinase\/FMN Cyclase Are Associated with Cataracts and Multisystem Disease","volume":"106","author":"Wortmann","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1111\/bjd.19481","article-title":"Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations","volume":"184","author":"Onoufriadis","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1002\/1873-3468.14309","article-title":"The TKFC Ala185Thr variant, reported as \u2018null\u2019 for fructose metabolism, is fully active as triokinase","volume":"596","author":"Ribeiro","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41440-018-0058-9","article-title":"Role of activating transcription factor 3 in fructose-induced metabolic syndrome in mice","volume":"41","author":"Chou","year":"2018","journal-title":"Hypertens. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"560","DOI":"10.2337\/diabetes.53.3.560","article-title":"Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice","volume":"53","author":"Matsuzaka","year":"2004","journal-title":"Diabetes"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.cmet.2009.01.011","article-title":"The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance","volume":"9","author":"Nagai","year":"2009","journal-title":"Cell Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1080\/1028415X.2018.1427659","article-title":"Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus of Wistar rats","volume":"22","author":"Batista","year":"2019","journal-title":"Nutr. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1017\/S0007114519001612","article-title":"Hepatic transcriptomics analysis reveals that fructose intervention down-regulated xenobiotics-metabolising enzymes through aryl hydrocarbon receptor signalling suppression in C57BL\/6N mice","volume":"122","author":"Pan","year":"2019","journal-title":"Br. J. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2337\/db08-0868","article-title":"Carbohydrate-responsive element-binding protein (ChREBP) is a negative regulator of ARNT\/HIF-1beta gene expression in pancreatic islet beta-cells","volume":"59","author":"Noordeen","year":"2010","journal-title":"Diabetes"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2165\/00003495-198600322-00003","article-title":"The polyol pathway. A historical review","volume":"32","author":"Clements","year":"1986","journal-title":"Drugs"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"106326","DOI":"10.1016\/j.phrs.2022.106326","article-title":"Polyol pathway and redox balance in diabetes","volume":"182","author":"Garg","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Singh, M., Kapoor, A., and Bhatnagar, A. (2021). Physiological and Pathological Roles of Aldose Reductase. Metabolites, 11.","DOI":"10.3390\/metabo11100655"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Sano, H., Nakamura, A., Yamane, M., Niwa, H., Nishimura, T., Araki, K., Takemoto, K., Ishiguro, K.I., Aoki, H., and Kato, Y. (2022). The polyol pathway is an evolutionarily conserved system for sensing glucose uptake. PLoS Biol., 20.","DOI":"10.1371\/journal.pbio.3001678"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1038\/ncomms3434","article-title":"Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome","volume":"4","author":"Lanaspa","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Qiu, L., Lin, J., Ying, M., Chen, W., Yang, J., Deng, T., Chen, J., Shi, D., and Yang, J.Y. (2013). Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073591"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.3892\/mmr.2017.6895","article-title":"Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines","volume":"16","author":"Shi","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.3892\/mmr.2017.6313","article-title":"Inhibition of aldose reductase ameliorates ethanol-induced steatosis in HepG2 cells","volume":"15","author":"Qiu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/toxsci\/kfx038","article-title":"Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver","volume":"163","author":"Le","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"270","DOI":"10.2310\/JIM.0b013e31827c2795","article-title":"Activation of carbohydrate response element-binding protein by ethanol","volume":"61","author":"Liangpunsakul","year":"2013","journal-title":"J. Investig. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/hep.27926","article-title":"Carbohydrate-responsive element-binding protein, Sirtuin 1, and ethanol metabolism: A complicated network in alcohol-induced hepatic steatosis","volume":"62","author":"Liangpunsakul","year":"2015","journal-title":"Hepatology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"E227","DOI":"10.1152\/ajpendo.90245.2008","article-title":"Regulation of the fructose transporter GLUT5 in health and disease","volume":"295","author":"Douard","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_105","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."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/7\/1778\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:10:36Z","timestamp":1760123436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/7\/1778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,5]]},"references-count":105,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["nu15071778"],"URL":"https:\/\/doi.org\/10.3390\/nu15071778","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,5]]}}}