Various Terpenoids Derived from Herbal and Dietary Plants Function as PPAR Modulators and Regulate Carbohydrate and Lipid Metabolism

Several herbal plants improve medical conditions. Such plants contain many bioactive phytochemicals. Terpenoids (also called “isoprenoids”) constitute one of the largest families of natural products accounting for more than 40,000 individual compounds of both primary and secondary metabolisms. In particular, terpenoids are contained in many herbal plants, and several terpenoids have been shown to be available for pharmaceutical applications, for example, artemisinin and taxol as malaria and cancer medicines, respectively. Various terpenoids are contained in many plants for not only herbal use but also dietary use. In this paper, we describe several bioactive terpenoids contained in herbal or dietary plants, which can modulate the activities of ligand-dependent transcription factors, namely, peroxisome proliferator-activated receptors (PPARs). Because PPARs are dietary lipid sensors that control energy homeostasis, daily eating of these terpenoids might be useful for the management for obesity-induced metabolic disorders, such as type 2 diabetes, hyperlipidemia, insulin resistance, and cardiovascular diseases

Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ), whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB) and/or c-Jun amino-terminal kinase (JNK). In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies

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

Roles of type II H+-PPases and PPsPase1/PECP2 in early developmental stages and PPi homeostasis of Arabidopsis thaliana

The regulation of intracellular pyrophosphate (PPi) level is crucial for proper morphogenesis across all taxonomic kingdoms. PPi is released as a byproduct from ~200 metabolic reactions, then hydrolyzed by either membrane-bound (H+-PPase) or soluble pyrophosphatases (PPases). In Arabidopsis, the loss of the vacuolar H+-PPase/FUGU5, a key enzyme in PPi homeostasis, results in delayed growth and a number of developmental defects, pointing to the importance of PPi homeostasis in plant morphogenesis. The Arabidopsis genome encodes several PPases in addition to FUGU5, such as PPsPase1/PECP2, VHP2;1 and VHP2;2, although their significance regarding PPi homeostasis remains elusive. Here, to assess their contribution, phenotypic analyses of cotyledon aspect ratio, palisade tissue cellular phenotypes, adaxial side pavement cell complexity, stomatal distribution, and etiolated seedling length were performed, provided that they were altered due to excess PPi in a fugu5 mutant background. Overall, our analyses revealed that the above five traits were unaffected in ppspase1/pecp2, vhp2;1 and vhp2;2 loss-of-function mutants, as well as in fugu5 mutant lines constitutively overexpressing PPsPase1/PECP2. Furthermore, metabolomics revealed that ppspase1/pecp2, vhp2;1 and vhp2;2 etiolated seedlings exhibited metabolic profiles comparable to the wild type. Together, these results indicate that the contribution of PPsPase1/PECP2, VHP2;1 and VHP2;2 to PPi levels is negligible in comparison to FUGU5 in the early stages of seedling development

キンサイボウ カラ ノ パラクリン インシ ニ ヨル シボウ サイボウ ブンカ セイギョ ニ カンスル ケンキュウ

京都大学0048新制・課程博士博士(農学)甲第12364号農博第1545号新制||農||924(附属図書館)学位論文||H18||N4122(農学部図書室)UT51-2006-J356京都大学大学院農学研究科応用生物科学専攻(主査)教授 矢野 秀雄, 教授 久米 新一, 教授 今井 裕学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDFA

Erucic Acid-Rich Yellow Mustard Oil Improves Insulin Resistance in KK-Ay Mice

Obesity is a major risk factor for some metabolic disorders including type 2 diabetes. Enhancement of peroxisome proliferator-activated receptor (PPAR) γ, a master regulator of adipocyte differentiation, is known to increase insulin-sensitive small adipocytes. In contrast, decreased PPARγ activity is also reported to improve insulin resistance. We have previously identified erucic acid as a novel natural component suppressing PPARγ transcriptional activity. In this study, we investigated the effect of erucic acid-rich yellow mustard oil (YMO) on obese/diabetic KK-Ay mice. An in vitro luciferase reporter assay and mesenchymal stem cell (MSC) differentiation assay revealed that 25 µg/mL YMO significantly inhibited PPARγ transcriptional activity and differentiation of MSCs into adipocytes but promoted their differentiation into osteoblasts. In KK-Ay mice, dietary intake of 7.0% (w/w) YMO significantly decreased the surrogate indexes for insulin resistance and the infiltration of macrophages into adipose tissue. Furthermore, 7.0% YMO increased bone mineral density. These results suggest that YMO can ameliorate obesity-induced metabolic disorders

Ferulic acid suppresses expression of tryptophan metabolic key enzyme indoleamine 2, 3-dioxygenase via NFκB and p38 MAPK in lipopolysaccharide-stimulated microglial cells

<p>Ferulic acid (FA) is a phenol compound found in plants that has anti-inflammatory properties. Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolic enzyme induced in immune cells, including glial cells, during inflammation. Enhanced IDO expression leads to reduced tryptophan levels and increased levels of toxic metabolites, including quinolinic acid. Therefore, inhibition of IDO expression may be effective in suppressing progression of neurodegenerative diseases. In this study, we examined the effect of FA in microglial cells on <i>IDO</i> expression levels and related inflammatory signal molecules. FA suppressed LPS-induced <i>IDO</i> mRNA expression and also suppressed nuclear translocation of NF-κB and phosphorylation of p38 MAPK. However, FA did not affect the production of LPS-induced inflammatory mediators and phosphorylation of JNK. Our results indicate that FA suppresses LPS-induced <i>IDO</i> mRNA expression, which may be mediated by inhibition of the NF-κB and p38 MAPK pathways in microglial cells.</p> <p>Ferulic acid suppresses lipopolysaccharide-induced ｍRNA expression of indoleamine 2,3-deoxygenase via inhibition of NFκB and p38 MAPK pathways in microglial cells.</p