リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Endogenous Fructose Metabolism Could Explain the Warburg Effect and the Protection of SGLT2 Inhibitors in Chronic Kidney Disease.」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Endogenous Fructose Metabolism Could Explain the Warburg Effect and the Protection of SGLT2 Inhibitors in Chronic Kidney Disease.

NAKAGAWA Takahiko 60641595 SANCHEZ-LOZADA Laura G. ANDRES-HERMANDO Ana KOJIMA Hideto 00225434 0000-0002-4781-2052 KASAHARA Masato RODRIGUEZ-ITURBE Bernardo BJORNSTAD Petter LANASPA Miguel A. JOHNSON Richard J. 滋賀医科大学

2021.06.16

概要

Chronic low-grade inflammation underlies the pathogenesis of non-communicable diseases, including chronic kidney diseases (CKD). Inflammation is a biologically active process accompanied with biochemical changes involving energy, amino acid, lipid and nucleotides. Recently, glycolysis has been observed to be increased in several inflammatory disorders, including several types of kidney disease. However, the factors initiating glycolysis remains unclear. Added sugars containing fructose are present in nearly 70 percent of processed foods and have been implicated in the etiology of many non-communicable diseases. In the kidney, fructose is transported into the proximal tubules via several transporters to mediate pathophysiological processes. Fructose can be generated in the kidney during glucose reabsorption (such as in diabetes) as well as from intra-renal hypoxia that occurs in CKD. Fructose metabolism also provides biosynthetic precursors for inflammation by switching the intracellular metabolic profile from mitochondrial oxidative phosphorylation to glycolysis despite the availability of oxygen, which is similar to the Warburg effect in cancer. Importantly, uric acid, a byproduct of fructose metabolism, likely plays a key role in favoring glycolysis by stimulating inflammation and suppressing aconitase in the tricarboxylic acid cycle. A consequent accumulation of glycolytic intermediates connects to the production of biosynthetic precursors, proteins, lipids, and nucleic acids, to meet the increased energy demand for the local inflammation. Here, we discuss the possibility of fructose and uric acid may mediate a metabolic switch toward glycolysis in CKD. We also suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors may slow the progression of CKD by reducing intrarenal glucose, and subsequently fructose levels.

この論文で使われている画像

参考文献

18. Nakagawa T, Johnson RJ, Andres-Hernando A, Roncal-Jimenez C, SanchezLozada LG, Tolan DR, et al. Fructose Production and Metabolism in the

Kidney. J Am Soc Nephrol (2020) 31(5):898–906. doi: 10.1681/ASN.

2019101015

19. Chen Z, Liu M, Li L, Chen L. Involvement of the Warburg Effect in NonTumor Diseases Processes. J Cell Physiol (2018) 233(4):2839–49. doi: 10.1002/

jcp.25998

20. Aoyama M, Isshiki K, Kume S, Chin-Kanasaki M, Araki H, Araki S, et al.

Fructose Induces Tubulointerstitial Injury in the Kidney of Mice. Biochem

Biophys Res Commun (2012) 419(2):244–9. doi: 10.1016/j.bbrc.2012.02.001

21. Cirillo P, Gersch MS, Mu W, Scherer PM, Kim KM, Gesualdo L, et al.

K e t o h e x o k i n as e - D e p e n d e n t M e t a b o l i s m o f F r u c t o s e I n d uc e s

Proinflammatory Mediators in Proximal Tubular Cells. J Am Soc Nephrol

(2009) 20(3):545–53. doi: 10.1681/ASN.2008060576

22. Glushakova O, Kosugi T, Roncal C, Mu W, Heinig M, Cirillo P, et al. Fructose

Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells. J Am Soc

Nephrol (2008) 19(9):1712–20. doi: 10.1681/ASN.2007121304

23. Shinozaki K, Kashiwagi A, Nishio Y, Okamura T, Yoshida Y, Masada M, et al.

Abnormal Biopterin Metabolism is a Major Cause of Impaired EndotheliumDependent Relaxation Through Nitric Oxide/O2- Imbalance in InsulinResistant Rat Aorta. Diabetes (1999) 48(12):2437–45. doi: 10.2337/

diabetes.48.12.2437

24. Nakagawa T. Uncoupling of the VEGF-Endothelial Nitric Oxide Axis in

Diabetic Nephropathy: An Explanation for the Paradoxical Effects of VEGF in

Renal Disease. Am J Physiol Renal Physiol (2007) 292(6):F1665–72. doi:

10.1152/ajprenal.00495.2006

25. Nakagawa T, Tanabe K, Croker BP, Johnson RJ, Grant MB, Kosugi T, et al.

Endothelial Dysfunction as a Potential Contributor in Diabetic Nephropathy.

Nat Rev Nephrol (2011) 7(1):36–44. doi: 10.1038/nrneph.2010.152

26. Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W, et al.

Hyperuricemia Induces Endothelial Dysfunction. Kidney Int (2005) 67

(5):1739–42. doi: 10.1111/j.1523-1755.2005.00273.x

27. Sanchez-Lozada LG, Lanaspa MA, Cristobal-Garcia M, Garcia-Arroyo F, Soto

V, Cruz-Robles D, et al. Uric Acid-Induced Endothelial Dysfunction is

Associated With Mitochondrial Alterations and Decreased Intracellular

ATP Concentrations. Nephron Exp Nephrol (2012) 121(3-4):e71–8. doi:

10.1159/000345509

28. Brezis M, Rosen S. Hypoxia of the Renal Medulla–Its Implications for Disease.

N Engl J Med (1995) 332(10):647–55. doi: 10.1056/NEJM199503093321006

29. Nangaku M. Chronic Hypoxia and Tubulointerstitial Injury: A Final

Common Pathway to End-Stage Renal Failure. J Am Soc Nephrol (2006) 17

(1):17–25. doi: 10.1681/ASN.2005070757

30. Grimm C, Wenzel A, Groszer M, Mayser H, Seeliger M, Samardzija M, et al.

HIF-1-Induced Erythropoietin in the Hypoxic Retina Protects Against LightInduced Retinal Degeneration. Nat Med (2002) 8(7):718–24. doi: 10.1038/

nm723

31. Liu J, Wei Q, Guo C, Dong G, Liu Y, Tang C, et al. Hypoxia, HIF, and

Associated Signaling Networks in Chronic Kidney Disease. Int J Mol Sci

(2017) 18(5):950. doi: 10.3390/ijms18050950

32. Park TJ, Reznick J, Peterson BL, Blass G, Omerbasic D, Bennett NC, et al.

Fructose-Driven Glycolysis Supports Anoxia Resistance in the Naked MoleRat. Science (2017) 356(6335):307–11. doi: 10.1126/science.aab3896

33. Mirtschink P, Krishnan J, Grimm F, Sarre A, Horl M, Kayikci M, et al. HIFDriven SF3B1 Induces KHK-C to Enforce Fructolysis and Heart Disease.

Nature (2015) 522(7557):444–9. doi: 10.1038/nature14508

34. Brownlee M. Biochemistry and Molecular Cell Biology of Diabetic

Complications. Nature (2001) 414(6865):813–20. doi: 10.1038/414813a

35. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al.

Normalizing Mitochondrial Superoxide Production Blocks Three Pathways of

Hyperglycaemic Damage. Nature (2000) 404(6779):787–90. doi: 10.1038/

35008121

Japan Society for the Promotion of Science (21K10284).

1. Morita M, Kanasaki K. Sodium-Glucose Cotransporter-2 Inhibitors for

Diabetic Kidney Disease: Targeting Warburg Effects in Proximal Tubular

Cells. Diabetes Metab (2020) 46(5):353–61. doi: 10.1016/j.diabet.2020.06.005

2. Huang Z, Hong Q, Zhang X, Xiao W, Wang L, Cui S, et al. Aldose Reductase

Mediates Endothelial Cell Dysfunction Induced by High Uric Acid

Concentrations. Cell Commun Signal (2017) 15(1):3. doi: 10.1186/s12964016-0158-6

3. Srivastava SK, Ramana KV, Bhatnagar A. Role of Aldose Reductase and

Oxidative Damage in Diabetes and the Consequent Potential for Therapeutic

Options. Endocr Rev (2005) 26(3):380–92. doi: 10.1210/er.2004-0028

4. Yamauchi A, Miyai A, Shimada S, Minami Y, Tohyama M, Imai E, et al.

Localization and Rapid Regulation of Na+/myo-inositol Cotransporter in Rat

Kidney. J Clin Invest (1995) 96(3):1195–201. doi: 10.1172/JCI118151

5. Andres-Hernando A, Li N, Cicerchi C, Inaba S, Chen W, Roncal-Jimenez C, et al.

Protective Role of Fructokinase Blockade in the Pathogenesis of Acute Kidney

Injury in Mice. Nat Commun (2017) 8:14181. doi: 10.1038/ncomms14181

6. Lanaspa MA, Ishimoto T, Cicerchi C, Tamura Y, Roncal-Jimenez CA, Chen

W, et al. Endogenous Fructose Production and Fructokinase Activation

Mediate Renal Injury in Diabetic Nephropathy. J Am Soc Nephrol (2014) 25

(11):2526–38. doi: 10.1681/ASN.2013080901

7. Bjornstad P, Lanaspa MA, Ishimoto T, Kosugi T, Kume S, Jalal D, et al.

Fructose and Uric Acid in Diabetic Nephropathy. Diabetologia (2015) 58

(9):1993–2002. doi: 10.1007/s00125-015-3650-4

8. Wang M, Chen WY, Zhang J, Gobejishvili L, Barve SS, McClain CJ, et al.

Elevated Fructose and Uric Acid Through Aldose Reductase Contribute to

Experimental and Human Alcoholic Liver Disease. Hepatology (2020) 72

(5):1617–37. doi: 10.1002/hep.31197

9. Francey C, Cros J, Rosset R, Creze C, Rey V, Stefanoni N, et al. The ExtraSplanchnic Fructose Escape After Ingestion of a Fructose-Glucose Drink: An

Exploratory Study in Healthy Humans Using a Dual Fructose Isotope Method.

Clin Nutr ESPEN (2019) 29:125–32. doi: 10.1016/j.clnesp.2018.11.008

10. Lanaspa MA, Ishimoto T, Li N, Cicerchi C, Orlicky DJ, Ruzycki P, et al.

Endogenous Fructose Production and Metabolism in the Liver Contributes to

the Development of Metabolic Syndrome. Nat Commun (2013) 4:2434. doi:

10.1038/ncomms3929

11. Lanaspa MA, Kuwabara M, Andres-Hernando A, Li N, Cicerchi C, Jensen T,

et al. High Salt Intake Causes Leptin Resistance and Obesity in Mice by

Stimulating Endogenous Fructose Production and Metabolism. Proc Natl

Acad Sci USA (2018) 115(12):3138–43. doi: 10.1073/pnas.1713837115

12. Johnson RJ, Perez-Pozo SE, Sautin YY, Manitius J, Sanchez-Lozada LG, Feig

DI, et al. Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause

Type 2 Diabetes? Endocr Rev (2009) 30(1):96–116. doi: 10.1210/er.2008-0033

13. Nakagawa T, Tuttle KR, Short RA, Johnson RJ. Hypothesis: Fructose-Induced

Hyperuricemia as a Causal Mechanism for the Epidemic of the Metabolic

Syndrome. Nat Clin Pract Nephrol (2005) 1(2):80–6. doi: 10.1038/

ncpneph0019

14. Gersch MS, Mu W, Cirillo P, Reungjui S, Zhang L, Roncal C, et al. Fructose, But

Not Dextrose, Accelerates the Progression of Chronic Kidney Disease. Am J

Physiol Renal Physiol (2007) 293(4):F1256–61. doi: 10.1152/ajprenal.00181.2007

15. Nakayama T, Kosugi T, Gersch M, Connor T, Sanchez-Lozada LG, Lanaspa

MA, et al. Dietary Fructose Causes Tubulointerstitial Injury in the Normal Rat

Kidney. Am J Physiol Renal Physiol (2010) 298(3):F712–20. doi: 10.1152/

ajprenal.00433.2009

16. Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, et al. A

Causal Role for Uric Acid in Fructose-Induced Metabolic Syndrome. Am J Physiol

Renal Physiol (2006) 290(3):F625–31. doi: 10.1152/ajprenal.00140.2005

17. Nakagawa T, Lanaspa MA, Millan IS, Fini M, Rivard CJ, Sanchez-Lozada LG,

et al. Fructose Contributes to the Warburg Effect for Cancer Growth. Cancer

Metab (2020) 8:16. doi: 10.1186/s40170-020-00222-9

Frontiers in Immunology | www.frontiersin.org

June 2021 | Volume 12 | Article 694457

Nakagawa et al.

Fructose Causes Chronic Kidney Disease

36. Giacco F, Brownlee M. Oxidative Stress and Diabetic Complications. Circ Res

(2010) 107(9):1058–70. doi: 10.1161/CIRCRESAHA.110.223545

37. Naudi A, Jove M, Ayala V, Cassanye A, Serrano J, Gonzalo H, et al. Cellular

Dysfunction in Diabetes as Maladaptive Response to Mitochondrial Oxidative

Stress. Exp Diabetes Res (2012) 2012:696215. doi: 10.1155/2012/696215

38. Sharma K. Mitochondrial Hormesis and Diabetic Complications. Diabetes

(2015) 64(3):663–72. doi: 10.2337/db14-0874

39. Akude E, Zherebitskaya E, Chowdhury SK, Smith DR, Dobrowsky RT,

Fernyhough P. Diminished Superoxide Generation Is Associated With

Respiratory Chain Dysfunction and Changes in the Mitochondrial

Proteome of Sensory Neurons From Diabetic Rats. Diabetes (2011) 60

(1):288–97. doi: 10.2337/db10-0818

40. Herlein JA, Fink BD, O’Malley Y, Sivitz WI. Superoxide and Respiratory

Coupling in Mitochondria of Insulin-Deficient Diabetic Rats. Endocrinology

(2009) 150(1):46–55. doi: 10.1210/en.2008-0404

41. Bugger H, Boudina S, Hu XX, Tuinei J, Zaha VG, Theobald HA, et al. Type 1

Diabetic Akita Mouse Hearts Are Insulin Sensitive But Manifest Structurally

Abnormal Mitochondria That Remain Coupled Despite Increased Uncoupling

Protein 3. Diabetes (2008) 57(11):2924–32. doi: 10.2337/db08-0079

42. Sas KM, Kayampilly P, Byun J, Nair V, Hinder LM, Hur J, et al. Tissue-Specific

Metabolic Reprogramming Drives Nutrient Flux in Diabetic Complications.

JCI Insight (2016) 1(15):e86976. doi: 10.1172/jci.insight.86976

43. Sharma K, Karl B, Mathew AV, Gangoiti JA, Wassel CL, Saito R, et al.

Metabolomics Reveals Signature of Mitochondrial Dysfunction in Diabetic

Kidney Disease. J Am Soc Nephrol (2013) 24(11):1901–12. doi: 10.1681/

ASN.2013020126

44. Torres VE, Harris PC, Pirson Y. Autosomal Dominant Polycystic Kidney

Disease. Lancet (2007) 369(9569):1287–301. doi: 10.1016/S0140-6736(07)

60601-1

45. Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Pema M, et al.

Defective Glucose Metabolism in Polycystic Kidney Disease Identifies a New

Therapeutic Strategy. Nat Med (2013) 19(4):488–93. doi: 10.1038/nm.3092

46. Chiaravalli M, Rowe I, Mannella V, Quilici G, Canu T, Bianchi V, et al. 2Deoxy-D-Glucose Ameliorates PKD Progression. J Am Soc Nephrol (2016) 27

(7):1958–69. doi: 10.1681/ASN.2015030231

47. Ding H, Jiang L, Xu J, Bai F, Zhou Y, Yuan Q, et al. Inhibiting Aerobic

Glycolysis Suppresses Renal Interstitial Fibroblast Activation and Renal

Fibrosis. Am J Physiol Renal Physiol (2017) 313(3):F561–75. doi: 10.1152/

ajprenal.00036.2017

48. Lan R, Geng H, Singha PK, Saikumar P, Bottinger EP, Weinberg JM, et al.

Mitochondrial Pathology and Glycolytic Shift During Proximal Tubule

Atrophy After Ischemic AKI. J Am Soc Nephrol (2016) 27(11):3356–67. doi:

10.1681/ASN.2015020177

49. Van Schaftingen E, Detheux M, Veiga da Cunha M. Short-Term Control of

Glucokinase Activity: Role of a Regulatory Protein. FASEB J (1994) 8(6):414–

9. doi: 10.1096/fasebj.8.6.8168691

50. Agius L, Peak M. Intracellular Binding of Glucokinase in Hepatocytes and

Translocation by Glucose, Fructose and Insulin. Biochem J (1993) 296(Pt

3):785–96. doi: 10.1042/bj2960785

51. Brown KS, Kalinowski SS, Megill JR, Durham SK, Mookhtiar KA. Glucokinase

Regulatory Protein may Interact With Glucokinase in the Hepatocyte

Nucleus. Diabetes (1997) 46(2):179–86. doi: 10.2337/diabetes.46.2.179

52. Niculescu L, Veiga-da-Cunha M, Van Schaftingen E. Investigation on the

Mechanism by Which Fructose, Hexitols and Other Compounds Regulate the

Translocation of Glucokinase in Rat Hepatocytes. Biochem J (1997) 321( Pt

1):239–46. doi: 10.1042/bj3210239

53. Dekkers CCJ, Gansevoort RT. Sodium-Glucose Cotransporter 2 Inhibitors:

Extending the Indication to Non-Diabetic Kidney Disease? Nephrol Dial

Transpl (2020) 35(Suppl 1):i33–42. doi: 10.1093/ndt/gfz264

54. Nespoux J, Vallon V. Renal Effects of SGLT2 Inhibitors: An Update. Curr

Opin Nephrol Hypertens (2020) 29(2):190–8. doi: 10.1097/MNH.

0000000000000584

55. Cai T, Ke Q, Fang Y, Wen P, Chen H, Yuan Q, et al. Sodium-Glucose

Cotransporter 2 Inhibition Suppresses HIF-1a-Mediated Metabolic Switch

From Lipid Oxidation to Glycolysis in Kidney Tubule Cells of Diabetic Mice.

Cell Death Dis (2020) 11(5):390. doi: 10.1038/s41419-020-2544-7

56. Li J, Liu H, Takagi S, Nitta K, Kitada M, Srivastava SP, et al. Renal Protective

Effects of Empagliflozin Via Inhibition of EMT and Aberrant Glycolysis in

Frontiers in Immunology | www.frontiersin.org

57.

58.

59.

60.

61.

62.

63.

64.

65.

66.

67.

68.

69.

70.

71.

72.

73.

Proximal Tubules. JCI Insight (2020) 5(6):e129034. doi: 10.1172/

jci.insight.129034

Abbas NAT, El Salem A, Awad MM. Empagliflozin, SGLT2 Inhibitor,

Attenuates Renal Fibrosis in Rats Exposed to Unilateral Ureteric

Obstruction: Potential Role of Klotho Expression. Naunyn Schmiedebergs

Arch Pharmacol (2018) 391(12):1347–60. doi: 10.1007/s00210-018-1544-y

Li Q, Li Y, Liang L, Li J, Luo D, Liu Q, et al. Klotho Negatively Regulated

Aerobic Glycolysis in Colorectal Cancer Via ERK/HIF1a Axis. Cell Commun

Signal (2018) 16(1):26. doi: 10.1186/s12964-018-0241-2

Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Heise T, Bizzotto R, et al. Shift

to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2

Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes.

Diabetes (2016) 65(5):1190–5. doi: 10.2337/db15-1356

Vidali S, Aminzadeh S, Lambert B, Rutherford T, Sperl W, Kofler B, et al.

Mitochondria: The Ketogenic Diet–a Metabolism-Based Therapy. Int J

Biochem Cell Biol (2015) 63:55–9. doi: 10.1016/j.biocel.2015.01.022

Mudaliar S, Alloju S, Henry RR. Can a Shift in Fuel Energetics Explain the

Beneficial Cardiorenal Outcomes in the EMPA-REG Outcome Study? A Unifying

Hypothesis Diabetes Care (2016) 39(7):1115–22. doi: 10.2337/dc16-0542

Packer M. Interplay of Adenosine Monophosphate-Activated Protein Kinase/

Sirtuin-1 Activation and Sodium Influx Inhibition Mediates the Renal Benefits

of Sodium-Glucose Co-Transporter-2 Inhibitors in Type 2 Diabetes: A Novel

Conceptual Framework. Diabetes Obes Metab (2020) 22(5):734–42. doi:

10.1111/dom.13961

Phadke G, Kaushal A, Tolan DR, Hahn K, Jensen T, Bjornstad P, et al. Osmotic

Nephrosis and Acute Kidney Injury Associated With Sglt2 Inhibitor Use: A Case

Report. Am J Kidney Dis (2020) 76(1):144–7. doi: 10.1053/j.ajkd.2020.01.015

O’Neill LA, Hardie DG. Metabolism of Inflammation Limited by AMPK and

Pseudo-Starvation. Nature (2013) 493(7432):346–55. doi: 10.1038/nature11862

Viola A, Munari F, Sanchez-Rodriguez R, Scolaro T, Castegna A. The

Metabolic Signature of Macrophage Responses. Front Immunol (2019)

10:1462. doi: 10.3389/fimmu.2019.01462

Malide D, Davies-Hill TM, Levine M, Simpson IA. Distinct Localization of GLUT1, -3, and -5 in Human Monocyte-Derived Macrophages: Effects of Cell Activation.

Am J Physiol (1998) 274(3):E516–26. doi: 10.1152/ajpendo.1998.274.3.E516

Jones N, Blagih J, Zani F, Rees A, Hill DG, Jenkins BJ, et al. Fructose

Reprogrammes Glutamine-Dependent Oxidative Metabolism to Support

LPS-induced Inflammation. Nat Commun (2021) 12(1):1209. doi: 10.1038/

s41467-021-21461-4

Choe JY, Kim SK. Quercetin and Ascorbic Acid Suppress Fructose-Induced

NLRP3 Inflammasome Activation by Blocking Intracellular Shuttling of

TXNIP in Human Macrophage Cell Lines. Inflammation (2017) 40(3):980–

94. doi: 10.1007/s10753-017-0542-4

Palsson-McDermott EM, O’Neill LA. The Warburg Effect Then and Now:

From Cancer to Inflammatory Diseases. Bioessays (2013) 35(11):965–73. doi:

10.1002/bies.201300084

Karmaus PWF, Herrada AA, Guy C, Neale G, Dhungana Y, Long L, et al.

Critical Roles of mTORC1 Signaling and Metabolic Reprogramming for MCSF-mediated Myelopoiesis. J Exp Med (2017) 214(9):2629–47. doi: 10.1084/

jem.20161855

Duran RV, Oppliger W, Robitaille AM, Heiserich L, Skendaj R, Gottlieb E,

et al. Glutaminolysis Activates Rag-mTORC1 Signaling. Mol Cell (2012) 47

(3):349–58. doi: 10.1016/j.molcel.2012.05.043

Wilson DF, Rumsey WL, Green TJ, Vanderkooi JM. The Oxygen Dependence

of Mitochondrial Oxidative Phosphorylation Measured by a New Optical

Method for Measuring Oxygen Concentration. J Biol Chem (1988) 263

(6):2712–8. doi: 10.1016/S0021-9258(18)69126-4

Semba H, Takeda N, Isagawa T, Sugiura Y, Honda K, Wake M, et al. HIF1alpha-PDK1 Axis-Induced Active Glycolysis Plays an Essential Role in

Macrophage Migratory Capacity. Nat Commun (2016) 7:11635. doi:

10.1038/ncomms11635

Conflict of Interest: ML, LS-L and RJ have equity in a start-up company

developing fructokinase inhibitors (Colorado Research Partners LLC). TN and

RJ also have equity with XORTX therapeutics which is developing novel xanthine

oxidase inhibitors. RJ is also a consultant for Horizon Pharmaceuticals, Inc. BR-I is

a recipient of the Cátedra Salvador Zubirán, Universidad Nacional de México and

Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán, Ciudad de

June 2021 | Volume 12 | Article 694457

Nakagawa et al.

Fructose Causes Chronic Kidney Disease

Copyright © 2021 Nakagawa, Sanchez-Lozada, Andres-Hernando, Kojima,

Kasahara, Rodriguez-Iturbe, Bjornstad, Lanaspa and Johnson. This is an openaccess article distributed under the terms of the Creative Commons Attribution

License (CC BY). The use, distribution or reproduction in other forums is permitted,

provided the original author(s) and the copyright owner(s) are credited and that the

original publication in this journal is cited, in accordance with accepted academic

practice. No use, distribution or reproduction is permitted which does not comply with

these terms.

México, Mexico. PB has acted as a consultant for AstraZeneca, Bayer, BristolMyers Squibb, Boehringer Ingelheim, Eli-Lilly, Sanofi, Novo Nordisk, and

Horizon Pharma. PB serves on the advisory boards of AstraZeneca, Boehringer

Ingelheim, Novo Nordisk and XORTX.

The remaining authors declare that the research was conducted in the absence of

any commercial or financial relationships that could be construed as a potential

conflict of interest.

Frontiers in Immunology | www.frontiersin.org

June 2021 | Volume 12 | Article 694457

...

参考文献をもっと見る