9‐Oxo‐10(E),12(Z),15(Z)‐Octadecatrienoic Acid Activates Peroxisome Proliferator‐Activated Receptor α in Hepatocytes

Abstract

The peroxisome proliferator-activated receptor (PPAR)α is mainly expressed in the liver and plays an important role in the regulation of lipid metabolism. It has been reported that PPARα activation enhances fatty acid oxidation and reduces fat storage. Therefore, PPARα agonists are used to treat dyslipidemia. In the present study, we found that 9-oxo-10(E),12(Z),15(Z)-octadecatrienoic acid (9-oxo-OTA), which is a α-linolenic acid (ALA) derivative, is present in tomato (Solanum lycopersicum) extract. We showed that 9-oxo-OTA activated PPARα and induced the mRNA expression of PPARα target genes in murine primary hepatocytes. These effects promoted fatty acid uptake and the secretion of β-hydroxybutyrate, which is one of the endogenous ketone bodies. We also demonstrated that these effects of 9-oxo-OTA were not observed in PPARα-knockout (KO) primary hepatocytes. To our knowledge, this is the first study to report that 9-oxo-OTA promotes fatty acid metabolism via PPARα activation and discuss its potential as a valuable food-derived compound for use in the management of dyslipidemia.

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

“…Therefore, KOT supplementation could significantly mitigate the increased liver TC and TG content induced by the HCD hyperlipidemia model. One recent study demonstrated that 9-oxo-10(E),12(Z),15(Z)-octadecatrienoic acid in tomato extract promotes fatty acid metabolism via PPARα activation in liver cells and has potential for use in the management of dyslipidemia [ 42 ]. In addition, 13-oxo-9(Z),11(E),15(Z)-octadecatrienoic acid in the extract of tomato induced PPARγ expression in adipose tissue and resulted in the regulation of adipogenesis [ 43 ].…”

Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions

“…The compounds of HPLC fractions and white adipose tissue were assessed using a LC-MS system as previously described[ 21 , 25 ]. Briefly, each HPLC fraction was dissolved in 1mL of extraction solvent (99.5% EtOH).…”

“…These interesting effects of tomato consumption have been elucidated, but the active compounds in tomato are not fully understood. In recent years, we demonstrated that tomato contained fatty acid derivatives (oxylipin) that activated lipid metabolism via peroxisome proliferator-activated receptor (PPAR) α activation[ 19 – 21 ], which is important for fatty acid oxidation[ 22 – 24 ]. Although the effect of compounds in tomato on lipid metabolism has been elucidated, little is known about the effect on glucose metabolism.…”

17( S ),18( R )‐epoxyeicosatetraenoic acid generated by cytochrome P450 BM‐3 from Bacillus megaterium inhibits the development of contact hypersensitivity via G‐protein‐coupled receptor 40‐mediated neutrophil suppression

“…In another example, the expression levels of the Cyp4a subfamily including Cyp4a10, Cyp4a12, and Cyp4a14 are upregulated by PPARα activation . Because PUFAs, polyphenols, and carotenoids are all potent PPARα ligands, expression levels of Cyp4a subfamily members might be regulated by dietary components which in turn control the production of 17( S ),18( R )‐EpETE and 17( R ),18( S )‐EpETE . These findings indicate that the efficacy of dietary ω3 PUFA can be regulated by various food components through the induction of CYP expression, followed by production of 17,18‐EpETE.…”