Cornel kyoto joint symposium (takahashi@kyoto)

257 views
184 views

Published on

These slides were used in "Cornell-Kyoto Joint Symposium" on 5th March 2013.

Published in: Health & Medicine, Business
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
257
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Cornel kyoto joint symposium (takahashi@kyoto)

  1. 1. Amelioration ofObesity And MetabolicDisordersby Food FactorsNobuyuki TakahashiTsuyoshi GotoTeruo KawadaLab of Molecular Functionof Food,Kyoto University
  2. 2. 16,311 DaysSince 9 Jul 1968.
  3. 3. 48,934 Meals16,311 DaysSince 9 Jul 1968.
  4. 4. We Need Healthy Meals Everyday.
  5. 5. We Love Fat.
  6. 6. Fatty Liver
  7. 7. There Are Many PeopleHaving Fatty Liver.
  8. 8. One of Three Japanese HasFatty Liver.
  9. 9. Fatty Liver PatientsHave Increased.
  10. 10. HealthyLiver
  11. 11. HealthyLiverFatty Liver(NAFLD)
  12. 12. HealthyLiverFatty Liver(NAFLD)NASH
  13. 13. HealthyLiverFatty Liver(NAFLD)NASHFibrosis
  14. 14. HealthyLiverFatty Liver(NAFLD)NASHFibrosisCancersFatty Liver Finally Progresses toHepatic Cancers.
  15. 15. HealthyLiverFatty Liver(NAFLD)NASHFibrosisCancersFatty Liver Finally Progresses toHepatic Cancers.
  16. 16. Fatty Liver Should BeImproved.
  17. 17. We Love Fat.
  18. 18. To Find Food FactorsImproving The Abnormalitiesin Lipid Metabolism
  19. 19. Nuclear Receptors Are Activated bySmall HydrophobicCompounds.NuclearReceptorLigandRetinoic Acid Receptor(RAR)Vitamin D Receptor (VDR)Estrogen Receptor (ER)etc.
  20. 20. NuclearReceptorLigandTarget GeneNuclear Receptors Are Activated bySmall HydrophobicCompounds.
  21. 21. Target GeneNuclearReceptorLigandNuclear Receptors Are Activated bySmall HydrophobicCompounds.
  22. 22. Target GeneTargetGeneProductsNuclearReceptorLigandNuclear Receptors Are Activated bySmall HydrophobicCompounds.
  23. 23. Target GeneFood FactorsNuclearReceptorTargetGeneProductsNuclear Receptors Are Activated bySmall HydrophobicCompounds.
  24. 24. Peroxisome Proliferator-activated Receptors (PPARs)Are Involved in Lipid Metabolism.
  25. 25. Insulin SensitivityInsulin SensitivityEnergy ConsumptionEnergy Consumption ?Energy Consumption ?Energy ConsumptionLipogenesis ?PPARgPPARdPPARaPeroxisome Proliferator-activated Receptors (PPARs)Are Involved in Lipid Metabolism.
  26. 26. Energy ConsumptionPPARaPeroxisome Proliferator-activated Receptors (PPARs)Are Involved in Lipid Metabolism.
  27. 27. Energy ConsumptionPPARa02505007501000cont bezaAOX mRNA01000200030004000cont bezaCPT-1 mRNARelativeExpression(%ofControl)Peroxisome Proliferator-activated Receptors (PPARs)Are Involved in Lipid Metabolism.
  28. 28. PPARa ActivationEnhancesFatty AcidOxidation in The Liver.
  29. 29. Identification ofTomato-derivedCompoundsActivating PPARaExample
  30. 30. 050010001500control RF54 RF55 RF56 RF57 RF58 RF59 GWRelativeLuciferaseActivity(%ofcontrol)RF57**We Found an Active FractionActivating PPARain Tomato EtOH Extract.
  31. 31. 050010001500control RF54 RF55 RF56 RF57 RF58 RF59 GWRelativeLuciferaseActivity(%ofcontrol)RF57**C18H30O3 (MW: 294)We Found an Active FractionActivating PPARain Tomato EtOH Extract.
  32. 32. Oxo-octadecadienoic Acids(ODAs) Were ResponsibleCompoundsin Tomato EtOH Extract.OCOOHOCOOH9-oxo-ODA13-oxo-ODA
  33. 33. 9-oxo-ODA DecreasedLipid Accumulationin Mouse Primary Hepatocytes.0* * *2030CellularTG(mg/gprotein)10GW7647 (nM)9-oxo-ODA (mM)- 10010 20- -- -
  34. 34. KK-Ay ObeseDiabetic ModelMiceHigh-fat-dietContaining 13-oxo-ODA (0.02 &0.05%)4 Weeks
  35. 35. The 13-oxo-ODA Feeding IncreasedmRNA Expression of Fatty Acidoxidation-related Genes in The Liver.control 0.02% 0.05%050100150200CPT-1 AOX FAT/CD36RelativeExpression(%ofcontrol)** *
  36. 36. 50 μmcontrolThe 13-oxo-ODA Feeding DecreasedLipid Accumulation in The Liver.
  37. 37. 50 μmcontrol50 μm0.02%50 μm0.05%The 13-oxo-ODA Feeding DecreasedLipid Accumulation in The Liver.
  38. 38. 0255075100control 0.02% 0.05%(mg/gLiver)**HepaticTGContentThe 13-oxo-ODA Feeding DecreasedLipid Accumulation in The Liver.
  39. 39. 050100150200control 0.02% 0.05%(mg/dL)**SerumTGLevelThe 13-oxo-ODA Feeding DecreasedPlasma Lipid Levels.
  40. 40. control 0.02% 0.05%37.037.538.038.5RectalTemperature(oC)**The 13-oxo-ODA Feeding IncreasedRectal Temperature.
  41. 41. HealthyLiver
  42. 42. HealthyLiverFatty Liver(NAFLD)High-fat-diet
  43. 43. Tomato-derived CompoundsPrevent Fatty LiverDevelopment.HealthyLiverFatty Liver(NAFLD)High-fat-diet9/13-oxo-ODAs
  44. 44. Analysis ofSpice-derivedCompoundsControllingHepatic Lipid MetabolismExample
  45. 45. Fenugreek Is A SpiceUsed in Indian Carry.
  46. 46. KK-Ay ObeseDiabetic Model MiceHigh-Fat-DietContainingFenugreek (2%)4 Weeks
  47. 47. ControlThe Fenugreek-feeding DecreasedLipid Accumulation in The Liver.
  48. 48. The Fenugreek-feeding DecreasedLipid Accumulation in The Liver.Control 2% fenugreek
  49. 49. **020406080100120140control 2% fenugreekHepaticTGContentThe Fenugreek-feeding DecreasedLipid Accumulation in The Liver.(mg/gliver)
  50. 50. The Fenugreek-feeding DecreasedSerum Lipid Levels.00.20.40.60.811.21.41.61.8Control 2% Fenu*SerumTGLevel(mmol/L)
  51. 51. 020406080100120140C 4 5 6 7 8 9 10 11 12 13 14 15Fraction No.TGaccumulation(%ofcontrol)**24-h Treated HepG2 CellsWhat Was A PossibleResponsible Compound ?in Fenugreek.
  52. 52. OOHOdiosgeninDiosgenin Was A PossibleResponsible Compoundin Fenugreek.
  53. 53. Diosgenin Was A PossibleResponsible Compoundin Fenugreek.01020304050601 2 5 10diosgenin (mM)****CellularTG(mg/mgprotein)024-h Treated HepG2 Cells
  54. 54. The Fenugreek-feeding ShowedNo Effect on Fatty AcidOxidation in The Liver.050100150RelativemRNAExpression(%ofcontrol)CPT-1 AOXcontrol2% fenu
  55. 55. The Balance BetweenSynthesis And Oxidationof Fatty Acid Is Important.
  56. 56. The Fenugreek-feeding InhibitedFatty Acid Synthesis-relatedGene Expression in The Liver.SREBP-1c*020406080100120140FAS SCD-1control2% fenu**ACCp=0.0605RelativemRNAExpression(%ofcontrol)*GPAT
  57. 57. The Fenugreek-feeding InhibitedFatty Acid Synthesis-relatedGene Expression in The Liver.SREBP-1c*020406080100120140FAS SCD-1control2% fenu**ACCp=0.0605RelativemRNAExpression(%ofcontrol)*GPAT
  58. 58. Liver-X-Receptor (LXR) Is Involvedin Hepatic Fatty Acid Synthesis.
  59. 59. Fatty Acid SynthesisIntestineCholesterol AbsorptionLXRaLiver-X-Receptor (LXR) Is Involvedin Hepatic Fatty Acid Synthesis.
  60. 60. Fatty Acid SynthesisLXRaLXRaSREBP1cLiver-X-Receptor (LXR) Is Involvedin Hepatic Fatty Acid Synthesis.
  61. 61. Fatty Acid SynthesisLXRaLXRaSREBP1cFAS ACCFatty Acid SynthesisLiver-X-Receptor (LXR) Is Involvedin Hepatic Fatty Acid Synthesis.
  62. 62. LXR ActivationEnhancesLipid Synthesis in TheLiver.
  63. 63. LXR InhibitionSuppressesLipid Synthesis in The Liver.
  64. 64. Diosgenin Inhibited The Activation ofLXR in HepG2 Hepatocytes.LuciferaseActivity(%ofcontrol)diosgenin0100200300400500600700*****T0901317 --+-+ + +2 5 10+124-h Treated HepG2 Cells
  65. 65. 0102030405060T0901317 (1 μM)5 10controldiosgenin (μM)****CellularTG(mg/mgprotein)Diosgenin Inhibited The Activation ofLXR in HepG2 Hepatocytes.24-h Treated HepG2 Cells
  66. 66. RelativemRNAExpression(%ofcontrol)0controlFAS mRNA****100200300400500T0901317 (1 μM)5 10diosgenin (μM)Diosgenin Inhibited The Activation ofLXR in HepG2 Hepatocytes.
  67. 67. HealthyLiver
  68. 68. HealthyLiverFatty Liver(NAFLD)High-fat-diet
  69. 69. Fenugreek Also PreventsFatty Liver Development.HealthyLiverFatty Liver(NAFLD)High-fat-dietFenugreek(Diosgenin)
  70. 70. Other ExamplesVarious Food-derived CompoundsControl Nuclear ReceptorActivities.
  71. 71. Isoprenolsin Herbal Plantsb-Cryptoxanthinein OrangesAuraptenein Citrus FruitsCapsaicinin Hot PeppersOther ExamplesVarious Food-derived CompoundsControl Nuclear ReceptorActivities.
  72. 72. Phytolinb-CryptoxanthineVarious Food-derived CompoundsControl Nuclear ReceptorActivities.
  73. 73. Various Food-derived CompoundsControl Nuclear ReceptorActivities.Phytolinb-Cryptoxanthine
  74. 74. Food FactorsCould ImproveThe MetabolicAbnormalities.
  75. 75. What Do YouEat, Today ?
  76. 76. Thanks !!!E-mail: nobu@kais.kyoto-u.ac.jp

×