Several herbal medicines improve hyperlipidemia, diabetes and cardiovascular diseases. However, the molecular mechanism underlying this improvement has not yet been clarified. In this study, we found that several isoprenols, common components of herbal plants, activate human peroxisome proliferator-activated receptors (PPARs) as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. Farnesol and geranylgeraniol that are typical isoprenols in herbs and fruits activated not only PPARQ Q but also PPARK K as determined using the chimera assay system. These compounds also activated full-length human PPARQ Q and PPARK K in CV1 cells. Moreover, these isoprenols upregulated the expression of some lipid metabolic target genes of PPARQ Q and PPARK K in 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These results suggest that herbal medicines containing isoprenols with dual action on both PPARQ Q and PPARK K can be of interest for the amelioration of lipid metabolic disorders associated with diabetes. ß

The cAMP-response element-binding protein-binding protein (CBP) and p300 are common coactivators for several transcriptional factors. It has been reported that both CBP and p300 are significant for the activation of peroxisome proliferator-activated receptor ␥ (PPAR␥), which is a crucial nuclear receptor in adipogenesis. However, it remains unclear whether CBP and/or p300 is physiologically essential to the activation of PPAR␥ in adipocytes and adipocyte differentiation. In this study, we investigated the physiological significance of CBP/ p300 in NIH3T3 cells transiently expressing PPAR␥ and CBP and in 3T3-L1 preadipocytes stably expressing CBP-or p300-specific ribozymes. In PPAR␥-transfected NIH3T3 cells, induction of expression of PPAR␥ target genes such as adipocyte fatty acid-binding protein (aP2) and lipoprotein lipase (LPL) by adding thiazolidinedione was enhanced, depending on the amount of a CBP expression plasmid transfected. Expression of aP2 and LPL genes, as well as glycerol-3-phosphate dehydrogenase activity and triacylglyceride accumulation after adipogenic induction, was largely suppressed in 3T3-L1 adipocytes expressing either the CBP-or p300-specific active ribozyme, but not in inactive ribozyme-expressing cells. These data suggest that both CBP and p300 are indispensable for the full activation of PPAR␥ and adipocyte differentiation and that CBP and p300 do not mutually complement in the process.

Abietic acid is one of the terpenoids, which are multifunctional natural compounds. It has been reported that abietic acid suppresses e¡ects on in£ammation. However, the mechanism underlying the anti-in£ammatory e¡ects remains unclear. The present work indicates that abietic acid suppresses the protein expression of tumor necrosis factor-K K and cyclooxygenase 2, which are involved in in£ammation, in lipopolysaccharidestimulated macrophages. Moreover, this e¡ect resembles that of thiazolidinedione, a synthetic peroxisome proliferator-activated receptor-Q Q (PPARQ Q) ligand. Indeed, abietic acid activates PPARQ Q in luciferase reporter assays. The activity of abietic acid induces PPARQ Q target gene expression in RAW264.7 macrophages and 3T3-L1 adipocytes. These data indicate that abietic acid is a PPARQ Q ligand and that its anti-in£ammatory e¡ect is partly due to the activation of PPARQ Q in stimulated macrophages. The present work suggests a novel possibility that abietic acid, a naturally occurring compound, can be used not only for anti-in£ammation but also for regulating lipid metabolism and atherosclerosis. ß

Compressed sensing (CS) reconstructions of under-sampled measurements generate missing data based on assumptions of image sparsity. Non-contrast time-of-flight MR angiography (TOF-MRA) is a good candidate for CS based acceleration, as MRA images feature bright trees of sparse vessels over a well-suppressed anatomical background signal. A short scan time derived from CS is beneficial for patients of moyamoya disease (MMD) because of the frequency of MR scans. The purpose of this study was to investigate the reliability of TOF-MRA with CS in the evaluation of MMD. Twenty-two patients were examined using TOF-MRA with CS (CS-TOF) and parallel imaging (PI-TOF). The acceleration factors were 3 (CS3) and 5 (CS5) for CS-TOF, and 3 (PI3) for PI-TOF. Two neuroradiologists evaluated the MMD grading according to stenosis/occlusion scores using the modified Houkin’s system, and the visibility of moyamoya vessels (MMVs) using a 3-point scale. Concordance was calculated with Cohen’s κ. The numbers of MMVs in the basal ganglia were compared using Bland-Altman analysis and Wilcoxon’s signed-rank tests. MRA scan times were 4:07, 3:53, and 2:42 for PI3, CS3, and CS5, respectively. CS-reconstruction completed within 10 minutes. MMD grading and MMV visibility scales showed excellent correlation (κ > .966). Although the number of MMVs was significantly higher in CS3 than in PI3 (p < .0001) and CS5 (p < .0001), Bland-Altman analysis showed a good agreement between PI3, CS3, and CS5. Compressed sensing can accelerate TOF-MRA with improved visualization of small collaterals in equivalent time (CS3) or equivalent results in a shorter scan time (CS5).

Sparse TOF can achieve better image quality relative to PI TOF at higher acceleration factors. The diagnostic quality of distal branches (A2/3, M4, P4) was maintained with Sp 6×, which achieved a shorter acquisition time less than half of PI 2×.