The document discusses how compounds derived from tomatoes, specifically 9-oxo-octadecadienoic acid (9-oxo-ODA) and 13-oxo-octadecadienoic acid (13-oxo-ODA), were found to activate peroxisome proliferator-activated receptor alpha (PPARα) and improve abnormalities in hepatic lipid metabolism. Mice fed a high-fat diet supplemented with 13-oxo-ODA showed decreased hepatic triglyceride accumulation, lower plasma triglyceride levels, and increased rectal temperature compared to controls. The tomato-derived compounds were therefore found to prevent fatty liver development.

1. Tomato-derived Compounds
Improve Abnormalities in
Hepatic Lipid Metabolism.

2. We Love Fat.

3. Fatty Liver
…

4. There Are Many People
Having Fatty Liver.

5. One of Three Japanese Has
Fatty Liver.

6. Fatty Liver Patients
Have Increased.

7. Healthy
Liver

8. Healthy
Liver
Fatty Liver
(NAFLD)

9. Healthy
Liver
Fatty Liver
(NAFLD)
NASH

10. Healthy
Liver
Fatty Liver
(NAFLD)
NASH
Fibrosis

11. Healthy
Liver
Fatty Liver
(NAFLD)
NASH
Fibrosis
Cancers
Fatty Liver Finally Progresses
to Hepatic Cancers.

12. Healthy
Liver
Fatty Liver
(NAFLD)
NASH
Fibrosis
Fatty Liver Finally Progresses
to Hepatic Cancers.
Cancers

13. Fatty Liver Should Be
Improved.

14. We Love Fat.

15. Nuclear Receptors Are Activated
by Small Hydrophobic
Compounds.
Nuclear
Receptor
Ligand
Retinoic Acid Receptor
(RAR)
Vitamin D Receptor (VDR)
Estrogen Receptor (ER)
etc.

16. Nuclear
Receptor
Nuclear Receptors Are Activated
by Small Hydrophobic
Compounds.
Ligand
Target Gene

17. Nuclear Receptors Are Activated
by Small Hydrophobic
Compounds.
Target Gene
Nuclear
Receptor
Ligand

18. Nuclear Receptors Are Activated
by Small Hydrophobic
Compounds.
Target Gene
Target
Gene
Products
Nuclear
Receptor
Ligand

19. Nuclear Receptors Are Activated
by Small Hydrophobic
Compounds.
Target Gene
Food-derived
Compound
Nuclear
Receptor
Target
Gene
Products

20. Peroxisome Proliferator-activated
Receptors (PPARs) Are Involved
in Lipid Metabolism.

21. Insulin Sensitivity
Insulin Sensitivity
Energy Consumption
Energy Consumption ?
Energy Consumption ?
Energy Consumption
Lipogenesis ?
PPARg
PPARdPPARa
Peroxisome Proliferator-activated
Receptors (PPARs) Are Involved
in Lipid Metabolism.

22. Peroxisome Proliferator-activated
Receptors (PPARs) Are Involved
in Lipid Metabolism.
Energy Consumption
PPARa

23. Peroxisome Proliferator-activated
Receptors (PPARs) Are Involved
in Lipid Metabolism.
0
250
500
750
1000
cont beza
AOX mRNA
relativeofcontrol(%)
Energy Consumption
PPARa
0
1000
2000
3000
4000
cont beza
CPT-1 mRNA
relativeofcontrol(%)

24. PPARa Activation
Enhances
Fatty Acid
Oxidation in the
Liver.

25. Trials to Identify
Tomato-derived
Compounds
Activating
PPARa

26. 0
500
1000
1500
control RF54 RF55 RF56 RF57 RF58 RF59 GW
RelativeLuciferaseActivity
(%ofcontrol)
RF57
*
*
We Identified
an Active Fraction Activating
PPARa
Using Tomato EtOH Extract.

27. 0
500
1000
1500
control RF54 RF55 RF56 RF57 RF58 RF59 GW
RelativeLuciferaseActivity
(%ofcontrol)
RF57
*
*
C18H30O3 (MW: 294)
We Identified
an Active Fraction Activating
PPARa
Using Tomato EtOH Extract.

28. Oxo-octadecadienoic Acids were
Responsible Compounds of
RF57.
O
COOH
9-oxo-ODA

29. Oxo-octadecadienoic Acids were
Responsible Compounds of
RF57.
O
COOH
O
COOH
9-oxo-ODA
13-oxo-ODA

30. 9-oxo-ODA Decreased
Lipid Accumulation
in Mouse Primary
Hepatocytes.
0
* * *
20
30
TGAccumulation
(mg/gprotein)
10
GW7647 (nM)
9-oxo-ODA (mM)
- 100
10 20- -
- -

31. KK-Ay Obese
Diabetic Model
mice
High-Fat-Diet
Containing 13-oxo-
ODA (0.02 &
0.05%)
4 Weeks

32. 50 μm
control
The 13-oxo-ODA Feeding
Decreased Hepatic TG
Accumulation.

33. 50 μm
control
50 μm
0.02%
50 μm
0.05%
The 13-oxo-ODA Feeding
Decreased Hepatic TG
Accumulation.

34. 0
25
50
75
100
control 0.02% 0.05%
(mg/gLiver)
*
The 13-oxo-ODA Feeding
Decreased Hepatic TG
Accumulation.
*

35. 0
50
100
150
200
control 0.02% 0.05%
(mg/dL)
*
The 13-oxo-ODA-fed Mice
Showed Lowering Plasma TG
Levels.
*

36. control 0.02% 0.05%
Rectal Temperature Was
Increased by the 13-oxo-ODA
Feeding.
37.0
37.5
38.0
38.5
RectalTemperature
(oC)
*
*

37. Healthy
Liver

38. Healthy
Liver
Fatty Liver
(NAFLD)
High-Fat-
Diet

39. Tomato-derived Compounds
Prevent Fatty Liver
Development.
Healthy
Liver
Fatty Liver
(NAFLD)
High-Fat-
Diet
9/13-oxo-
ODAs

40. Tomato Contains
Various Bioactive
Compounds.

41. More Tomatoes ...

42. More Tomatoes ...

43. More Tomatoes ...
Thanks !!!
E-mail: nobu@kais.kyoto-
u.ac.jp