1932

Abstract

The consumption of fructose as sugar and high-fructose corn syrup has markedly increased during the past several decades. This trend coincides with the exponential rise of metabolic diseases, including obesity, nonalcoholic fatty liver disease, cardiovascular disease, and diabetes. While the biochemical pathways of fructose metabolism were elucidated in the early 1990s, organismal-level fructose metabolism and its whole-body pathophysiological impacts have been only recently investigated. In this review, we discuss the history of fructose consumption, biochemical and molecular pathways involved in fructose metabolism in different organs and gut microbiota, the role of fructose in the pathogenesis of metabolic diseases, and the remaining questions to treat such diseases.

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2022-08-22
2024-03-28
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Literature Cited

  1. 1.
    Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R et al. 2010. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 51:1961–71
    [Google Scholar]
  2. 2.
    Ahn IS, Lang JM, Olson CA, Diamante G, Zhang G et al. 2020. Host genetic background and gut microbiota contribute to differential metabolic responses to fructose consumption in mice. J. Nutr. 150:2716–28
    [Google Scholar]
  3. 3.
    Andres-Hernando A, Cicerchi C, Kuwabara M, Orlicky DJ, Sanchez-Lozada LG et al. 2021. Umami-induced obesity and metabolic syndrome is mediated by nucleotide degradation and uric acid generation. Nat. Metab. 3:1189–201
    [Google Scholar]
  4. 4.
    Andres-Hernando A, Li N, Cicerchi C, Inaba S, Chen W et al. 2017. Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice. Nat. Commun. 8:14181
    [Google Scholar]
  5. 5.
    Barone S, Fussell SL, Singh AK, Lucas F, Xu J et al. 2009. Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J. Biol. Chem. 284:5056–66
    [Google Scholar]
  6. 6.
    Bartley C, Brun T, Oberhauser L, Grimaldi M, Molica F et al. 2019. Chronic fructose renders pancreatic β-cells hyper-responsive to glucose-stimulated insulin secretion through extracellular ATP signaling. Am. J. Physiol. Endocrinol. Metab. 317:E25–41
    [Google Scholar]
  7. 7.
    Beisner J, Gonzalez-Granda A, Basrai M, Damms-Machado A, Bischoff SC. 2020. Fructose-induced intestinal microbiota shift following two types of short-term high-fructose dietary phases. Nutrients 12:3444
    [Google Scholar]
  8. 8.
    Bier A, Braun T, Khasbab R, Di Segni A, Grossman E et al. 2018. A high salt diet modulates the gut microbiota and short chain fatty acids production in a salt-sensitive hypertension rat model. Nutrients 10:1154
    [Google Scholar]
  9. 9.
    Blakemore SJ, Aledo JC, James J, Campbell FC, Lucocq JM, Hundal HS. 1995. The GLUT5 hexose transporter is also localized to the basolateral membrane of the human jejunum. Biochem. J. 309:Part 17–12
    [Google Scholar]
  10. 10.
    Blanco ABG. 2017. Carbohydrate Metabolism London: Medical Biochemistry Academic
  11. 11.
    Brütting C, Lara Bisch M, Brandsch C, Hirche F, Stangl GI 2021. Impact of dietary propionate on fructose-induced changes in lipid metabolism, gut microbiota and short-chain fatty acids in mice. Int. J. Food Sci. Nutr. 72:160–73
    [Google Scholar]
  12. 12.
    Burant CF, Takeda J, Brot-Laroche E, Bell GI, Davidson NO. 1992. Fructose transporter in human spermatozoa and small intestine is GLUT5. J. Biol. Chem. 267:14523–26
    [Google Scholar]
  13. 13.
    Busserolles J, Gueux E, Rock E, Demigné C, Mazur A, Rayssiguier Y. 2003. Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. J. Nutr. 133:1903–8
    [Google Scholar]
  14. 14.
    Cani PD, de Vos WM. 2017. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front. Microbiol. 8:1765
    [Google Scholar]
  15. 15.
    Carreno DV, Corro NB, Cerda-Infante JF, Echeverria CE, Asencio-Barria CA et al. 2021. Dietary fructose promotes prostate cancer growth. Cancer Res 81:2824–32
    [Google Scholar]
  16. 16.
    Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM et al. 2012. The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55:2005–23
    [Google Scholar]
  17. 17.
    Charrez B, Qiao L, Hebbard L. 2015. The role of fructose in metabolism and cancer. Horm. Mol. Biol. Clin. Investig. 22:79–89
    [Google Scholar]
  18. 18.
    Cheeseman CI. 1993. GLUT2 is the transporter for fructose across the rat intestinal basolateral membrane. Gastroenterology 105:1050–56
    [Google Scholar]
  19. 19.
    Chen WL, Wang YY, Zhao A, Xia L, Xie G et al. 2016. Enhanced fructose utilization mediated by SLC2A5 is a unique metabolic feature of acute myeloid leukemia with therapeutic potential. Cancer Cell 30:779–91
    [Google Scholar]
  20. 20.
    Choi YJ, Shin HS, Choi HS, Park JW, Jo I et al. 2014. Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab. Investig. 94:1114–25
    [Google Scholar]
  21. 21.
    Coyte KZ, Rakoff-Nahoum S. 2019. Understanding competition and cooperation within the mammalian gut microbiome. Curr. Biol. 29:R538–44
    [Google Scholar]
  22. 22.
    Cozma AI, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V et al. 2012. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes Care 35:1611–20
    [Google Scholar]
  23. 23.
    Cui XL, Schlesier AM, Fisher EL, Cerqueira C, Ferraris RP. 2005. Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 288:G1310–20
    [Google Scholar]
  24. 24.
    Cummings BP, Stanhope KL, Graham JL, Evans JL, Baskin DG et al. 2010. Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: amelioration by the antioxidant, α-lipoic acid. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298:R1343–50
    [Google Scholar]
  25. 25.
    Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. 2016. Prevalence of inflammatory bowel disease among adults aged ≥18 years – United States, 2015. MMWR Morb. Mortal. Wkly. Rep. 65:1166–69
    [Google Scholar]
  26. 26.
    De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C et al. 2014. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156:84–96
    [Google Scholar]
  27. 27.
    DeBosch BJ, Chen Z, Saben JL, Finck BN, Moley KH. 2014. Glucose transporter 8 (GLUT8) mediates fructose-induced de novo lipogenesis and macrosteatosis. J. Biol. Chem. 289:10989–98
    [Google Scholar]
  28. 28.
    Depommier C, Everard A, Druart C, Plovier H, Van Hul M et al. 2019. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25:1096–103
    [Google Scholar]
  29. 29.
    Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA et al. 2016. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167:1339–53.e21
    [Google Scholar]
  30. 30.
    Dhingra R, Sullivan L, Jacques PF, Wang TJ, Fox CS et al. 2007. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 116:480–88
    [Google Scholar]
  31. 31.
    Diggle CP, Shires M, Leitch D, Brooke D, Carr IM et al. 2009. Ketohexokinase: expression and localization of the principal fructose-metabolizing enzyme. J. Histochem. Cytochem. 57:763–74
    [Google Scholar]
  32. 32.
    Dixon A, Robertson K, Yung A, Que M, Randall H et al. 2020. Efficacy of probiotics in patients of cardiovascular disease risk: a systematic review and meta-analysis. Curr. Hypertens. Rep. 22:74
    [Google Scholar]
  33. 33.
    Do MH, Lee E, Oh M-J, Kim Y, Park H-Y. 2018. High-glucose or -fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change. Nutrients 10:761
    [Google Scholar]
  34. 34.
    Doridot L, Hannou SA, Krawczyk SA, Tong W, Kim M-S et al. 2021. A systems approach dissociates fructose-induced liver triglyceride from hypertriglyceridemia and hyperinsulinemia in male mice. Nutrients 13:3642
    [Google Scholar]
  35. 35.
    Dotimas JR, Lee AW, Schmider AB, Carroll SH, Shah A et al. 2016. Diabetes regulates fructose absorption through thioredoxin-interacting protein. eLife 5:e18313
    [Google Scholar]
  36. 36.
    Douard V, Ferraris RP. 2008. Regulation of the fructose transporter GLUT5 in health and disease. Am. J. Physiol. Endocrinol. Metab. 295:E227–37
    [Google Scholar]
  37. 37.
    Drozdowski LA, Thomson AB. 2006. Intestinal sugar transport. World J. Gastroenterol. 12:1657–70
    [Google Scholar]
  38. 38.
    Duboc H, Rajca S, Rainteau D, Benarous D, Maubert M-A et al. 2013. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62:531–39
    [Google Scholar]
  39. 39.
    Egli L, Lecoultre V, Theytaz F, Campos V, Hodson L et al. 2013. Exercise prevents fructose-induced hypertriglyceridemia in healthy young subjects. Diabetes 62:2259–65
    [Google Scholar]
  40. 40.
    Fan L, Gao W, Nguyen BV, Jefferson JR, Liu Y et al. 2020. Impaired renal hemodynamics and glomerular hyperfiltration contribute to hypertension-induced renal injury. Am. J. Physiol. Ren. Physiol. 319:F624–35
    [Google Scholar]
  41. 41.
    Fan Y, Pedersen O. 2021. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19:55–71
    [Google Scholar]
  42. 42.
    Farias DP, de Araújo FF, Neri-Numa IA, Pastore GM 2019. Prebiotics: trends in food, health and technological applications. Trends Food Sci. Technol. 93:23–35
    [Google Scholar]
  43. 43.
    Febbraio MA, Karin M. 2021.. “ Sweet death”: fructose as a metabolic toxin that targets the gut-liver axis. Cell Metab 33:2316–28
    [Google Scholar]
  44. 44.
    Ferreira DF, Fiamoncini J, Prist IH, Ariga SK, de Souza HP, de Lima TM. 2015. Novel role of TLR4 in NAFLD development: modulation of metabolic enzymes expression. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1851:1353–59
    [Google Scholar]
  45. 45.
    Flegal KM, Carroll MD, Ogden CL, Curtin LR. 2010. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303:235–41
    [Google Scholar]
  46. 46.
    Fu X, Liu Z, Zhu C, Mou H, Kong Q. 2019. Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit. Rev. Food Sci. Nutr. 59:S130–52
    [Google Scholar]
  47. 47.
    Fukui H. 2016. Increased intestinal permeability and decreased barrier function: Does it really influence the risk of inflammation?. Inflamm. Intest. Dis. 1:135–45
    [Google Scholar]
  48. 48.
    Gaby AR. 2005. Adverse effects of dietary fructose. Altern. Med. Rev. 10:294–306
    [Google Scholar]
  49. 49.
    Gersch MS, Mu W, Cirillo P, Reungjui S, Zhang L et al. 2007. Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am. J. Physiol. Ren. Physiol. 293:F1256–61
    [Google Scholar]
  50. 50.
    Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang SK et al. 2019. High-fructose corn syrup enhances intestinal tumor growth in mice. Science 363:1345–49
    [Google Scholar]
  51. 51.
    Gopher A, Vaisman N, Mandel H, Lapidot A. 1990. Determination of fructose metabolic pathways in normal and fructose-intolerant children: a 13C NMR study using [U-13C]fructose. PNAS 87:5449–53
    [Google Scholar]
  52. 52.
    Goran MI, Ulijaszek SJ, Ventura EE. 2013. High fructose corn syrup and diabetes prevalence: a global perspective. Glob. Public Health 8:55–64
    [Google Scholar]
  53. 53.
    Gouyon F, Caillaud L, Carriere V, Klein C, Dalet V et al. 2003. Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: a study in GLUT2-null mice. J. Physiol. 552:823–32
    [Google Scholar]
  54. 54.
    Guynn RW, Veloso D, Veech RL. 1972. The concentration of malonyl-coenzyme A and the control of fatty acid synthesis in vivo. J. Biol. Chem. 247:7325–31
    [Google Scholar]
  55. 55.
    Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T et al. 2019. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metab 30:67–77.e3
    [Google Scholar]
  56. 56.
    Hanover LM, White JS. 1993. Manufacturing, composition, and applications of fructose. Am. J. Clin. Nutr. 58:724S–32S
    [Google Scholar]
  57. 57.
    Harris DS, Slot JW, Geuze HJ, James DE. 1992. Polarized distribution of glucose transporter isoforms in Caco-2 cells. PNAS 89:7556–60
    [Google Scholar]
  58. 58.
    Hayasaki T, Ishimoto T, Doke T, Hirayama A, Soga T et al. 2019. Fructose increases the activity of sodium hydrogen exchanger in renal proximal tubules that is dependent on ketohexokinase. J. Nutr. Biochem. 71:54–62
    [Google Scholar]
  59. 59.
    Heinz F, Lamprecht W, Kirsch J. 1968. Enzymes of fructose metabolism in human liver. J. Clin. Investig. 47:1826–32
    [Google Scholar]
  60. 60.
    Helwig U, Koch AK, Reichel C, Jessen P, Buning J et al. 2021. A prospective multicenter study on the prevalence of fructose malabsorption in patients with chronic inflammatory bowel disease. Digestion 102:397–403
    [Google Scholar]
  61. 61.
    Herman MA, Birnbaum MJ. 2021. Molecular aspects of fructose metabolism and metabolic disease. Cell Metab 33:2329–54
    [Google Scholar]
  62. 62.
    Higuchi BS, Rodrigues N, Gonzaga MI, Paiolo JCC, Stefanutto N et al. 2018. Intestinal dysbiosis in autoimmune diabetes is correlated with poor glycemic control and increased interleukin-6: a pilot study. Front. Immunol. 9:1689
    [Google Scholar]
  63. 63.
    Hsu C-N, Lin Y-J, Hou C-Y, Tain Y-L. 2018. Maternal administration of probiotic or prebiotic prevents male adult rat offspring against developmental programming of hypertension induced by high fructose consumption in pregnancy and lactation. Nutrients 10:1229
    [Google Scholar]
  64. 64.
    Hsu CN, Chang-Chien GP, Lin S, Hou CY, Tain YL. 2019. Targeting on gut microbial metabolite trimethylamine-N-oxide and short-chain fatty acid to prevent maternal high-fructose-diet-induced developmental programming of hypertension in adult male offspring. Mol. Nutr. Food Res. 63:e1900073
    [Google Scholar]
  65. 65.
    Hui H, Huang D, McArthur D, Nissen N, Boros LG, Heaney AP. 2009. Direct spectrophotometric determination of serum fructose in pancreatic cancer patients. Pancreas 38:706–12
    [Google Scholar]
  66. 66.
    Ishimoto T, Lanaspa MA, Le MT, Garcia GE, Diggle CP et al. 2012. Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice. PNAS 109:4320–25
    [Google Scholar]
  67. 67.
    Jaiswal N, Agrawal S, Agrawal A. 2019. High fructose-induced metabolic changes enhance inflammation in human dendritic cells. Clin. Exp. Immunol. 197:237–49
    [Google Scholar]
  68. 68.
    Jang C, Hui S, Lu W, Cowan AJ, Morscher RJ et al. 2018. The small intestine converts dietary fructose into glucose and organic acids. Cell Metab 27:351–61.e3
    [Google Scholar]
  69. 69.
    Jang C, Wada S, Yang S, Gosis B, Zeng X et al. 2020. The small intestine shields the liver from fructose-induced steatosis. Nat. Metab. 2:586–93
    [Google Scholar]
  70. 70.
    Jensen T, Abdelmalek MF, Sullivan S, Nadeau KJ, Green M et al. 2018. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. J. Hepatol. 68:1063–75
    [Google Scholar]
  71. 71.
    Jia L, Jia Q, Yang J, Jia R, Zhang H. 2018. Efficacy of probiotics supplementation on chronic kidney disease: a systematic review and meta-analysis. Kidney Blood Press. Res. 43:1623–35
    [Google Scholar]
  72. 72.
    Jirillo E, Caccavo D, Magrone T, Piccigallo E, Amati L et al. 2002. The role of the liver in the response to LPS: experimental and clinical findings. J. Endotoxin Res. 8:319–27
    [Google Scholar]
  73. 73.
    Jones N, Blagih J, Zani F, Rees A, Hill DG et al. 2021. Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation. Nat. Commun. 12:1209
    [Google Scholar]
  74. 74.
    Kaplan RS, Mayor JA, Johnston N, Oliveira DL. 1990. Purification and characterization of the reconstitutively active tricarboxylate transporter from rat liver mitochondria. J. Biol. Chem. 265:13379–85
    [Google Scholar]
  75. 75.
    Khan S, Waliullah S, Godfrey V, Khan MAW, Ramachandran RA et al. 2020. Dietary simple sugars alter microbial ecology in the gut and promote colitis in mice. Sci. Transl. Med. 12:eaay6218
    [Google Scholar]
  76. 76.
    Khangwal I, Shukla P. 2019. Potential prebiotics and their transmission mechanisms: recent approaches. J. Food Drug Anal. 27:649–56
    [Google Scholar]
  77. 77.
    Kim J, Kang J, Kang YL, Woo J, Kim Y et al. 2020. Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer. Nat. Commun. 11:5436
    [Google Scholar]
  78. 78.
    Kim M, Astapova II, Flier SN, Hannou SA, Doridot L et al. 2017. Intestinal, but not hepatic, ChREBP is required for fructose tolerance. JCI Insight 2:e96703
    [Google Scholar]
  79. 79.
    Kim MS, Krawczyk SA, Doridot L, Fowler AJ, Wang JX et al. 2016. ChREBP regulates fructose-induced glucose production independently of insulin signaling. J. Clin. Investig. 126:4372–86
    [Google Scholar]
  80. 80.
    Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K et al. 2013. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4:1829
    [Google Scholar]
  81. 81.
    Kinoshita M, Suzuki Y, Saito Y. 2002. Butyrate reduces colonic paracellular permeability by enhancing PPARγ activation. Biochem. Biophys. Res. Commun. 293:827–31
    [Google Scholar]
  82. 82.
    Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. 2016. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165:1332–45
    [Google Scholar]
  83. 83.
    Kranhold JF, Loh D, Morris RC Jr. 1969. Renal fructose-metabolizing enzymes: significance in hereditary fructose intolerance. Science 165:402–3
    [Google Scholar]
  84. 84.
    Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. 2014. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 146:726–35
    [Google Scholar]
  85. 85.
    Lambertz J, Weiskirchen S, Landert S, Weiskirchen R. 2017. Fructose: a dietary sugar in crosstalk with microbiota contributing to the development and progression of non-alcoholic liver disease. Front. Immunol. 8:1159
    [Google Scholar]
  86. 86.
    Lanaspa MA, Andres-Hernando A, Orlicky DJ, Cicerchi C, Jang C et al. 2018. Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice. J. Clin. Investig. 128:2226–38
    [Google Scholar]
  87. 87.
    Lanaspa MA, Ishimoto T, Cicerchi C, Tamura Y, Roncal-Jimenez CA et al. 2014. Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy. J. Am. Soc. Nephrol. 25:2526–38
    [Google Scholar]
  88. 88.
    Larsson SC, Bergkvist L, Wolk A. 2006. Consumption of sugar and sugar-sweetened foods and the risk of pancreatic cancer in a prospective study. Am. J. Clin. Nutr. 84:1171–76
    [Google Scholar]
  89. 89.
    Li J-M, Yu R, Zhang L-P, Wen S-Y, Wang S-J et al. 2019. Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: a benefit of short-chain fatty acids. Microbiome 7:98
    [Google Scholar]
  90. 90.
    Li J, Jia H, Cai X, Zhong H, Feng Q et al. 2014. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32:834–41
    [Google Scholar]
  91. 91.
    Liu H, Huang D, McArthur DL, Boros LG, Nissen N, Heaney AP. 2010. Fructose induces transketolase flux to promote pancreatic cancer growth. Cancer Res 70:6368–76
    [Google Scholar]
  92. 92.
    Liu J, Zhuang ZJ, Bian DX, Ma XJ, Xun YH et al. 2014. Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice. Clin. Exp. Pharmacol. Physiol. 41:482–88
    [Google Scholar]
  93. 93.
    Liu L, Li T, Liao Y, Wang Y, Gao Y et al. 2020. Triose kinase controls the lipogenic potential of fructose and dietary tolerance. Cell Metab 32:605–18.e7
    [Google Scholar]
  94. 94.
    Liu Z, Zaki MH, Vogel P, Gurung P, Finlay BB et al. 2012. Role of inflammasomes in host defense against Citrobacter rodentium infection. J. Biol. Chem. 287:16955–64
    [Google Scholar]
  95. 95.
    Louis P, Hold GL, Flint HJ. 2014. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. 12:661–72
    [Google Scholar]
  96. 96.
    Lowette K, Roosen L, Tack J, Vanden Berghe P. 2015. Effects of high-fructose diets on central appetite signaling and cognitive function. Front. Nutr. 2:5
    [Google Scholar]
  97. 97.
    Lu J, Hou X, Yuan X, Cui L, Liu Z et al. 2018. Knockout of the urate oxidase gene provides a stable mouse model of hyperuricemia associated with metabolic disorders. Kidney Int 93:69–80
    [Google Scholar]
  98. 98.
    Mai BH, Yan LJ. 2019. The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders. Diabetes Metab. Syndr. Obes. 12:821–26
    [Google Scholar]
  99. 99.
    Malik VS, Popkin BM, Bray GA, Despres JP, Willett WC, Hu FB. 2010. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care 33:2477–83
    [Google Scholar]
  100. 100.
    Marriott BP, Cole N, Lee E 2009. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J. Nutr. 139:1228S–35S
    [Google Scholar]
  101. 101.
    McLarty JL, Marsh SA, Chatham JC. 2013. Post-translational protein modification by O-linked N-acetyl-glucosamine: its role in mediating the adverse effects of diabetes on the heart. Life Sci 92:621–27
    [Google Scholar]
  102. 102.
    Mellor KM, Bell JR, Wendt IR, Davidoff AJ, Ritchie RH, Delbridge LM. 2011. Fructose modulates cardiomyocyte excitation-contraction coupling and Ca2+ handling in vitro. PLOS ONE 6:e25204
    [Google Scholar]
  103. 103.
    Mellor KM, Ritchie RH, Davidoff AJ, Delbridge LM. 2010. Elevated dietary sugar and the heart: experimental models and myocardial remodeling. Can. J. Physiol. Pharmacol. 88:525–40
    [Google Scholar]
  104. 104.
    Michaud DS, Liu S, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. 2002. Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J. Natl. Cancer Inst. 94:1293–300
    [Google Scholar]
  105. 105.
    Mirmonsef P, Zariffard MR, Gilbert D, Makinde H, Landay AL, Spear GT. 2012. Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with Toll-like receptor ligands. Am. J. Reprod. Immunol. 67:391–400
    [Google Scholar]
  106. 106.
    Mirtschink P, Krishnan J, Grimm F, Sarre A, Horl M et al. 2015. HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease. Nature 522:444–49
    [Google Scholar]
  107. 107.
    Montrose DC, Nishiguchi R, Basu S, Staab HA, Zhou XK et al. 2021. Dietary fructose alters the composition, localization, and metabolism of gut microbiota in association with worsening colitis. Cell. Mol. Gastroenterol. Hepatol. 11:525–50
    [Google Scholar]
  108. 108.
    Nishiguchi R, Basu S, Staab HA, Ito N, Zhou XK et al. 2021. Dietary interventions to prevent high-fructose diet-associated worsening of colitis and colitis-associated tumorigenesis in mice. Carcinogenesis 42:842–52
    [Google Scholar]
  109. 109.
    Olsen NJ, Heitmann BL. 2009. Intake of calorically sweetened beverages and obesity. Obes. Rev. 10:68–75
    [Google Scholar]
  110. 110.
    Oppelt SA, Sennott EM, Tolan DR. 2015. Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans. Mol. Genet. Metab. 114:445–50
    [Google Scholar]
  111. 111.
    Ottman N, Reunanen J, Meijerink M, Pietilä TE, Kainulainen V et al. 2017. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLOS ONE 12:e0173004
    [Google Scholar]
  112. 112.
    Park D-Y, Ahn Y-T, Huh C-S, McGregor RA, Choi M-S. 2013. Dual probiotic strains suppress high fructose-induced metabolic syndrome. World J. Gastroenterol. 19:274–83
    [Google Scholar]
  113. 113.
    Park YK, Yetley EA. 1993. Intakes and food sources of fructose in the United States. Am. J. Clin. Nutr. 58:737S–47S
    [Google Scholar]
  114. 114.
    Patel C, Douard V, Yu S, Tharabenjasin P, Gao N, Ferraris RP. 2015. Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309:R499–509
    [Google Scholar]
  115. 115.
    Payne AN, Chassard C, Lacroix C. 2012. Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity. Obes. Rev. 13:799–809
    [Google Scholar]
  116. 116.
    Peng L, Li Z-R, Green RS, Holzman IR, Lin J. 2009. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 139:1619–25
    [Google Scholar]
  117. 117.
    Pereira GV, Abdel-Hamid AM, Dutta S, D'Alessandro-Gabazza CN, Wefers D et al. 2021. Degradation of complex arabinoxylans by human colonic Bacteroidetes. Nat. Commun. 12:459
    [Google Scholar]
  118. 118.
    Perrar I, Buyken AE, Penczynski KJ, Remer T, Kuhnle GG et al. 2021. Relevance of fructose intake in adolescence for fatty liver indices in young adulthood. Eur. J. Nutr. 60:3029–41
    [Google Scholar]
  119. 119.
    Rivière A, Gagnon M, Weckx S, Roy D, De Vuyst L. 2015. Mutual cross-feeding interactions between Bifidobacterium longum subsp. longum NCC2705 and Eubacterium rectale ATCC 33656 explain the bifidogenic and butyrogenic effects of arabinoxylan oligosaccharides. Appl. Environ. Microbiol. 81:7767–81
    [Google Scholar]
  120. 120.
    Rodenbach KE, Schneider MF, Furth SL, Moxey-Mims MM, Mitsnefes MM et al. 2015. Hyperuricemia and progression of CKD in children and adolescents: the Chronic Kidney Disease in Children (CKiD) cohort study. Am. J. Kidney Dis. 66:984–92
    [Google Scholar]
  121. 121.
    Roncal-Jimenez CA, Ishimoto T, Lanaspa MA, Milagres T, Hernando AA et al. 2016. Aging-associated renal disease in mice is fructokinase dependent. Am. J. Physiol. Ren. Physiol. 311:F722–30
    [Google Scholar]
  122. 122.
    Rumessen JJ, Gudmand-Hoyer E. 1986. Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Gut 27:1161–68
    [Google Scholar]
  123. 123.
    Salguero MV, Al-Obaide MAI, Singh R, Siepmann T, Vasylyeva TL. 2019. Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp. Ther. Med. 18:3461–69
    [Google Scholar]
  124. 124.
    Sánchez B, Delgado S, Blanco-Míguez A, Lourenço A, Gueimonde M, Margolles A. 2017. Probiotics, gut microbiota, and their influence on host health and disease. Mol. Nutr. Food Res. 61:1600240
    [Google Scholar]
  125. 125.
    Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. 2019. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat. Rev. Gastroenterol. Hepatol. 16:605–16
    [Google Scholar]
  126. 126.
    Schernhammer ES, Hu FB, Giovannucci E, Michaud DS, Colditz GA et al. 2005. Sugar-sweetened soft drink consumption and risk of pancreatic cancer in two prospective cohorts. Cancer Epidemiol. Biomarkers Prev. 14:2098–105
    [Google Scholar]
  127. 127.
    Schiattarella GG, Sannino A, Toscano E, Giugliano G, Gargiulo G et al. 2017. Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis. Eur. Heart J. 38:2948–56
    [Google Scholar]
  128. 128.
    Schulze MB, Manson JE, Ludwig DS, Colditz GA, Stampfer MJ et al. 2004. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA 292:927–34
    [Google Scholar]
  129. 129.
    Shoham DA, Durazo-Arvizu R, Kramer H, Luke A, Vupputuri S et al. 2008. Sugary soda consumption and albuminuria: results from the National Health and Nutrition Examination Survey, 1999–2004. PLOS ONE 3:e3431
    [Google Scholar]
  130. 130.
    Shuster J, Jenkins A, Logan C, Barnett T, Riehle R et al. 1992. Soft drink consumption and urinary stone recurrence: a randomized prevention trial. J. Clin. Epidemiol. 45:911–16
    [Google Scholar]
  131. 131.
    Softic S, Cohen DE, Kahn CR. 2016. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig. Dis. Sci. 61:1282–93
    [Google Scholar]
  132. 132.
    Song M. 2019. Dietary fructose induced gut microbiota dysbiosis is an early event in the onset of metabolic phenotype. FASEB J 33:S1723.2
    [Google Scholar]
  133. 133.
    Sprinz C, Altmayer S, Zanon M, Watte G, Irion K et al. 2018. Effects of blood glucose level on 18F-FDG uptake for PET/CT in normal organs: a systematic review. PLOS ONE 13:e0193140
    [Google Scholar]
  134. 134.
    Takasaki Y. 1966. Studies on sugar-isomerizing enzyme. Agric. Biol. Chem. 30:1247–53
    [Google Scholar]
  135. 135.
    Taylor EN, Curhan GC. 2008. Fructose consumption and the risk of kidney stones. Kidney Int 73:207–12
    [Google Scholar]
  136. 136.
    Taylor SR, Ramsamooj S, Liang RJ, Katti A, Pozovskiy R et al. 2021. Dietary fructose improves intestinal cell survival and nutrient absorption. Nature 597:263–67
    [Google Scholar]
  137. 137.
    Thirunavukkarasu V, Anitha Nandhini AT, Anuradha CV 2004. Effect of α-lipoic acid on lipid profile in rats fed a high-fructose diet. Exp. Diabesity Res. 5:195–200
    [Google Scholar]
  138. 138.
    Ulevitch RJ, Tobias PS. 1999. Recognition of Gram-negative bacteria and endotoxin by the innate immune system. Curr. Opin. Immunol. 11:19–22
    [Google Scholar]
  139. 139.
    Utzschneider KM, Kahn SE. 2006. The role of insulin resistance in nonalcoholic fatty liver disease. J. Clin. Endocrinol. Metab. 91:4753–61
    [Google Scholar]
  140. 140.
    van der Beek CM, Dejong CHC, Troost FJ, Masclee AAM, Lenaerts K. 2017. Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and mucosal protection and healing. Nutr. Rev. 75:286–305
    [Google Scholar]
  141. 141.
    Volynets V, Spruss A, Kanuri G, Wagnerberger S, Bischoff SC, Bergheim I. 2010. Protective effect of bile acids on the onset of fructose-induced hepatic steatosis in mice. J. Lipid Res. 51:3414–24
    [Google Scholar]
  142. 142.
    Wang Y, Kirpich I, Liu Y, Ma Z, Barve S et al. 2011. Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. Am. J. Pathol. 179:2866–75
    [Google Scholar]
  143. 143.
    Wang Y, Qi W, Song G, Pang S, Peng Z et al. 2020. High-fructose diet increases inflammatory cytokines and alters gut microbiota composition in rats. Mediat. Inflamm. 2020:6672636
    [Google Scholar]
  144. 144.
    Weng Y, Fan X, Bai Y, Wang S, Huang H et al. 2018. SLC2A5 promotes lung adenocarcinoma cell growth and metastasis by enhancing fructose utilization. Cell Death Discov 4:38
    [Google Scholar]
  145. 145.
    White JS. 2008. Straight talk about high-fructose corn syrup: what it is and what it ain't. Am. J. Clin. Nutr. 88:1716S–21S
    [Google Scholar]
  146. 146.
    Yki-Jarvinen H, Luukkonen PK, Hodson L, Moore JB. 2021. Dietary carbohydrates and fats in nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol. 18:770–86
    [Google Scholar]
  147. 147.
    Zhang M, Wang C, Wang C, Zhao H, Zhao C et al. 2015. Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease. J. Nutr. Biochem. 26:337–44
    [Google Scholar]
  148. 148.
    Zhao S, Jang C, Liu J, Uehara K, Gilbert M et al. 2020. Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature 579:586–91
    [Google Scholar]
  149. 149.
    Zubiría MG, Gambaro SE, Rey MA, Carasi P, Serradell MdLÁ, Giovambattista A 2017. Deleterious metabolic effects of high fructose intake: the preventive effect of Lactobacillus kefiri administration. Nutrients 9:470
    [Google Scholar]
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