Time filter

Source Type

Takatsuki, Japan

Osaka University of Pharmaceutical science is a private university in Takatsuki, Osaka, Japan. The predecessor of the school was founded in 1904, and it was chartered as a university in 1950. Wikipedia.

Fujimori K.,Osaka University of Pharmaceutical Sciences
PPAR Research

Adipocytes and fat cells play critical roles in the regulation of energy homeostasis. Adipogenesis (adipocyte differentiation) is regulated via a complex process including coordinated changes in hormone sensitivity and gene expression. PPARγ is a ligand-dependent transcription factor and important in adipogenesis, as it enhances the expression of numerous adipogenic and lipogenic genes in adipocytes. Prostaglandins (PGs), which are lipid mediators, are associated with the regulation of PPARγ function in adipocytes. Prostacyclin promotes the differentiation of adipocyte-precursor cells to adipose cells via activation of the expression of C/EBPβ and δ. These proteins are important transcription factors in the activation of the early phase of adipogenesis, and they activate the expression of PPARγ, which event precedes the maturation of adipocytes. PGEand PGFstrongly suppress the early phase of adipocyte differentiation by enhancing their own production via receptor-mediated elevation of the expression of cycloxygenase-2, and they also suppress the function of PPARγ. In contrast, PGDand its non-enzymatic metabolite, Δ12-PGJ2, activate the middle-late phase of adipocyte differentiation through both DP2 receptors and PPARγ. This paper focuses on potential roles of PGs as PPARγ modulators in adipogenesis and regulators of obesity. © 2012 Ko Fujimori. Source

Ohno Y.,Osaka University of Pharmaceutical Sciences
Central Nervous System Agents in Medicinal Chemistry

The serotonergic system plays a crucial role in regulating psychoemotional, cognitive and motor functions in the central nervous system (CNS). Among 5-HT receptor inftypes, 5-HT1A receptors have long been implicated in the pathogenesis and treatment of anxiety and depressive disorders. 5-HT1A receptors function as both presynaptic (autorecep-tor) and postsynaptic receptors in specific brain regions such as the limbic areas, septum and raphe nuclei. 5-HT1A receptors negatively regulate cAMP-dependent signal transduction and inhibit neuronal activity by opening G-protein-gated inwardly rectifying potassium channels. The therapeutic action of 5-HT1A agonists and their mechanism in alleviating anxiety and depressive disorders have been well documented. In addition, recent studies have revealed new insights into the therapeutic role of 5-HT1A receptors in treating various CNS disorders, including not only depressive disorders (e.g., delayed onset of action and refractory symptoms), but also schizophrenia (e.g., cognitive impairment and antipsychotic-induced extrapyramidal side effects) and Parkinson's disease (e.g., extrapyramidal motor symptoms and L-DOPA-induced dyskinesia). These lines of evidences encourage us to design new generation 5-HT1A ligands such as 5-HT1A agonists with greater potency, higher selectivity and improved pharmacokinetic properties, and 5-HT1A ligands which combine multiple pharmacological actions (e.g., inhibition of serotonin transporter, dopamine D2 receptors and other 5-HT receptor inftypes). Such new 5-HT1A ligands may overcome clinical efficacy limitations and/or improve adverse reactions in current CNS therapies. © 2010 Bentham Science Publishers Ltd. Source

Prostaglandin (PG) F 2α suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferator-activated receptor γ. In this study, we identified a novel suppression mechanism, operating in the early phase of adipogenesis, that increased the production of anti-adipogenic PGF 2α and PGE 2 by enhancing cyclooxygenase (COX) 2 expression through the PGF 2α-activated FP receptor/extracellular-signal-regulated kinase (ERK)/cyclic AMP response element binding protein (CREB) cascade. COX-2 expression was enhanced with a peak at 1 h for the mRNA level and at 3 h for the protein level after the addition of Fluprostenol, an FP receptor agonist. The Fluprostenol-derived elevation of COX-2 expression was suppressed by the co-treatment with an FP receptor antagonist, AL8810, with a mitogen-activated protein kinase (MEK; ERK kinase) inhibitor, PD98059. ERK was phosphorylated within 10 min after the addition of Fluprostenol, and its phosphorylation was inhibited by the co-treatment with AL8810 or PD98059. Moreover, FP receptor mediated activation of the MEK/ERK cascade and COX-2 expression increased the production of PGF 2α and PGE 2. An FP receptor antagonist and each inhibitor for MEK and COX-2 suppressed the PGF 2α-derived induction of synthesis of these PGs. Furthermore, promoter-luciferase and chromatin immunoprecipitation assays demonstrated that PGF 2α- derived COX-2 expression was activated through binding of CREB to the promoter region of the COX-2 gene in 3T3-L1 cells. These results indicate that PGF 2α suppresses the progression of the early phase of adipogenesis by enhancing the binding of CREB to the COX-2 promoter via FP receptor activated MEK/ERK cascade. Thus, PGF 2α forms a positive feedback loop that coordinately suppresses the early phase of adipogenesis through the increased production of anti-adipogenic PGF 2α and PGE 2. © 2011 FEBS. Source

Kobayashi T.,Osaka University of Pharmaceutical Sciences | Fujimori K.,Osaka University of Pharmaceutical Sciences
American Journal of Physiology - Endocrinology and Metabolism

Here, we show that Elovl3 (elongation of very long-chain fatty acids 3) was involved in the regulation of the progression of adipogenesis through activation of peroxisome proliferator-activated receptor (PPAR)7 in mouse adipocytic 3T3-L1 cells. The expression of the Elovl3 gene increased during adipogenesis, the expression pattern of which was similar to that of the PPAR7 gene. Troglitazone, a PPAR7 agonist, enhanced Elovl3 expression in adipocytes, as it did that of other PPAR7 target genes. Promoter-reporter analysis demonstrated that three PPAR-responsive elements in the Elovl3 gene promoter had the potential to activate its expression in 3T3-L1 cells. Moreover, a chromatin immunoprecipitation assay revealed that PPAR7 bound these PPAR-responsive elements of the Elovl3 promoter. When the Elovl3 mRNA level was suppressed by its siRNAs, the level of intracellular triglycerides was significantly decreased, and the expression levels of adipogenic, lipolytic, and lipogenic genes were also repressed. In a mammalian two-hybrid assay, C18:1 and C20:1 very long-chain fatty acids (VLCFAs), which are the products of Elovl3 and activated PPAR7 function. In addition, these same VLCFAs could prevent the Elovl3 siRNA-mediated suppression of adipogenesis by enhancing the expression of adipogenic, lipolytic, and lipogenic genes in adipocytes. Moreover, this VLCFAs-mediated activation was repressed by a PPAR7 antagonist. These results indicate that the expression of the Elovl3 gene was activated by PPAR7 during adipogenesis. Elovl3-produced C18:1 and C20:1 VLCFAs acted as agonists of PPAR7 in 3T3-L1 cells. Thus, the Elovl3-PPAR7 cascade is a novel regulatory circuit for the regulation of adipogenesis through improvement of PPAR7 function in adipocytes. © 2012 the American Physiological Society. Source

Ono M.,Osaka University of Pharmaceutical Sciences | Fujimori K.,Osaka University of Pharmaceutical Sciences
Journal of Agricultural and Food Chemistry

Adipocyte differentiation (adipogenesis) is a complex process including the coordinated changes in hormone sensitivity and gene expression in response to various stimuli. Natural compounds are known to be involved in the regulation of this process. Here we investigated the effects of dietary apigenin, a plant flavonoid, on adipogenesis. Apigenin suppressed adipocyte differentiation of mouse adipocytic 3T3-L1 cells and reduced the accumulation of intracellular lipids. Quantitative PCR and Western blot analyses revealed that apigenin decreased the levels of peroxisome proliferator-activated receptor γ and its target genes such as fatty acid binding protein 4 (aP2) and stearoyl-CoA desaturase. Apigenin decreased or had no effect on the expression of lipolytic genes such as adipose triglyceride lipase, hormone sensitive lipase, and monoacyl glyceride lipase, thereby reducing glycerol release from adipocytes. Noteworthily, apigenin activated 5′-adenosine monophosphate-activated protein kinase (AMPK) in an apigenin dose-dependent manner, which activation is known to suppress adipogenesis. These results provide a novel insight into the molecular mechanism involved in the action of apigenin: the apigenin-induced activation of AMPK leads to decreased expression of adipogenic and lipolytic genes, thus suppressing adipogenesis in 3T3-L1 cells. Thus, dietary apigenin may contribute to lower body-fat content and body-weight gain through the activation of AMPK. © 2011 American Chemical Society. Source

Discover hidden collaborations