Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.

Comparative and stability analyses of 9- and 13-Oxo-octadecadienoic acids in various species of tomato.

Peroxisome proliferator-activated receptor-α (PPARα) regulates lipid metabolism. We have reported that tomato fruit contains 9-Oxo-(10E,12E)-octadecadienoic acid (9-Oxo-(10E,12E)-ODA), a PPARα agonist. In this study, we found that various tomato samples contained 9-Oxo-(10E,12Z)-ODA and its 13-Oxo-ODA isomers. Furthermore, several isomers showed structural stability under hot and acidic conditions.

9-oxo-10(E),12(E)-Octadecadienoic acid derived from tomato is a potent PPAR α agonist to decrease triglyceride accumulation in mouse primary hepatocytes.

SCOPE: Tomato is one of the most common crops worldwide and contains many beneficial compounds that improve abnormalities of lipid metabolism. However, the molecular mechanism underlying the effect of tomato on lipid metabolism is unclear. It has been commonly accepted that peroxisome proliferator-activated receptor α (PPARα) is one of the most important targets for ameliorating abnormalities of lipid metabolism. Therefore, we focused on the activation of PPARα and attempted to detect active compounds activating PPARα in tomato. METHODS AND RESULTS: To identify such active compounds, we screened fractions of tomato extracts using PPARα luciferase reporter assay. One fraction, rechromatographed-fraction eluted in 57 min (RF57), significantly increased PPARα reporter activity, in which a single compound is detected by LC/MS analysis. On the basis of LC/MS and NMR analyses, we determined the chemical structure of the active compound in RF57 as 9-oxo-10(E),12(E)-octadecadienoic acid (9-oxo-ODA). The RF57 fraction significantly increased the mRNA expression levels of PPARα target genes involved in fatty acid oxidation and O(2) consumption in mouse primary hepatocytes. Furthermore, RF57 inhibited cellular triglyceride accumulation in the hepatocytes. CONCLUSION: These findings suggest that tomatoes containing 9-oxo-ODA that acts on PPARα are valuable for ameliorating abnormalities of lipid metabolism.

Coexpression analysis of tomato genes and experimental verification of coordinated expression of genes found in a functionally enriched coexpression module.

Gene-to-gene coexpression analysis is a powerful approach to infer the function of uncharacterized genes. Here, we report comprehensive identification of coexpression gene modules of tomato (Solanum lycopersicum) and experimental verification of coordinated expression of module member genes. On the basis of the gene-to-gene correlation coefficient calculated from 67 microarray hybridization data points, we performed a network-based analysis. This facilitated the identification of 199 coexpression modules. A gene ontology annotation search revealed that 75 out of the 199 modules are enriched with genes associated with common functional categories. To verify the coexpression relationships between module member genes, we focused on one module enriched with genes associated with the flavonoid biosynthetic pathway. A non-enzyme, non-transcription factor gene encoding a zinc finger protein in this module was overexpressed in S. lycopersicum cultivar Micro-Tom, and expression levels of flavonoid pathway genes were investigated. Flavonoid pathway genes included in the module were up-regulated in the plant overexpressing the zinc finger gene. This result demonstrates that coexpression modules, at least the ones identified in this study, represent actual transcriptional coordination between genes, and can facilitate the inference of tomato gene function.

Antihypertensive effect of a gamma-aminobutyric acid rich tomato cultivar 'DG03-9' in spontaneously hypertensive rats.

This study aimed to investigate the effects of a gamma-aminobutyric acid (GABA) rich tomato (Solanum lycopersicum L.) cultivar 'DG03-9' in comparison with 'Momotaro', a commonly consumed tomato cultivar in Japan, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). In a single administration study, treatment with the GABA-rich cultivar elicited a significant decrease in SBP compared to the control group. In a chronic administration study, SHR were fed diets containing one of the tomato cultivars for 4 weeks. Both cultivars significantly reduced the increase in SBP compared to the control. The antihypertensive effect of the GABA-rich cultivar was higher than that of the commonly consumed cultivar in both the single- and chronic-administration studies. Treatment with a comparable amount of GABA elicited a similar response to treatment with the GABA-rich cultivar. These results suggest that the GABA-rich cultivar 'DG03-9' is a potent antihypertensive food and may be useful for treating hypertension effectively.