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Sorghum (Sorghum bicolor) is an essential cereal crop grown worldwide, rich in phytochemicals with potential health benefits for humans. In this study, the anti-diabetic effect of sorghum extract was investigated by treating 3T3-L1 cells with water-soluble fraction (SE) isolated from sorghum extract. SE did not affect the lipid accumulation of 3T3-L1 adipocytes induced with isobutyl methylxanthine/dexamethasone/insulin (MDI), but it significantly enhanced MDI/thiazolidincdiones (TZDs)-induced adipogenesis in 3T3-L1 adipocyte differentiation. Realtime RT-PCR showed that SE suppressed adipocyte specific genes and transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα), in both MDI- and MDI/TZDs-treated 3T3-L1 adipocytes. Furthermore, SE did not suppress PPARγ (Ser273) phosphorylation induced by MDI/Troglitazone treatment in 3T3-L1 adipocytes. SE treatment increased peroxisome proliferator-activated receptor α (PPARα) protein expression in MDI/TZD-induced 3T3-L1 adipocytes. SE likely promotes insulin sensitivity and lipid metabolism in 3T3-L1 preadipocytes by cooperating with TZDs independent of PPARγ (Ser273) expression. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor a (PPARa) is a ligand-activated transcription factor that plays an important role in the regulation of lipid metabolism. Previously, we identified paraprobiotic Lactobacillus amylovorus CPI 563 (CP1563) as having the highest PPARa agonist activity among numerous bacterial strains that included Bifidobacteria and Lactobacilli species. We also reported that treatment with fragmented CP 1563 improves lipid metabolism in a diet-induced obese mouse model, as well as levels of a lipid metabolism marker in people with body mass indices greater than or equal to 23 hut less than 30, which includes individuals classified as having class T obesity according to the guidelines of the Japan Society for the Study of Obesity. The purpose of this study was to elucidate the underlying mechanism by which CP1563 improves lipid metabolism. Using aPPARa luciferase reporter assay, we screened fractions of the ethanolic extract of CP 1563 for PPARa agonist activity. We subsequently identified 10-hydroxyoctadecanoic acid (10-HOA) as the main component responsible for the PPARa agonist activity using Nuclear Magnetic Resonance and X-ray crystal structure analysis. Furthermore, we investigated the effects of 10-HOA on obesity and lipid metabolism dysfunction in obese mice fed a high-fat diet Administration of 10-HOAfor 15 weeks decreased the level of abdominal visceral fat and improved plasma lipid metabolism in diet-induced obese mice. In conclusion, our results reveal that 10-HOA is an active component of CPI563 that is responsible for the improvement of lipid metabolism. Our findings are valuable for understanding the mechanisms that underlie the health benefits of paraprobiotics. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that are activated by endogenous fatty acids and synthetic compounds as ligands. We have been developing new phenylpropanoic acid derivatives based on structure-activity relationship studies that could reduce the side effects of existing clinical drugs. As a result, we have obtained many partial agonists that exhibit a moderate transcriptional activity while maintaining high specificity towards the receptors. However, because most of them are poorly soluble, protein-ligand interaction information has not yet been obtained by X-ray crystallography, which is essential for structure-activity relationship studies. In this paper, we report our ongoing crystallization experiments, which are aimed to develope a crystallization method for PPAR LBDs in solid-phase hydrogels that enables high-throughput protein-ligand complex crystal structure determination, using poorly soluble ligands.

Diesel exhaust (DE) is one of the air pollutants in the world, and exposure to DE is an environmental health concern. Most studies amongst the limited number of studies on hepatotoxicity have focused on genotoxicity or mutagenicity. However, DE exposure may cause liver damage because one prospective study suggests that DE exposure is associated with increased mortality due to arteriosclerosis and cirrhosis of the liver. Peroxisome proliferator-activated receptor (PPAR) α plays a role in the regulation of lipid homeostasis and inflammation and thereby may be involved in the progression of atherosclerosis. We investigated whether nanoparticle-rich diesel exhaust (NR-DE) affects the liver and how PPARα is involved in the NR-DE induced effects. We report these results briefly in this minireview. Our results suggest NR-DE-induced hepatic inflammation and dyslipidemia. PPARα may be involved in the development of these disorders.

Arteriosclerosis and allergy are increasingly common diseases. The pathogeneses are both based on changes in lifestyle and chronic inflammation. Herein we discuss cross talk between the two seemingly unrelated diseases, focusing on obesity and various related molecules, including adipokines, peroxisome proliferator-activated receptors (PPARs), C reactive protein (CRP), and soluble adhesion molecules.