gw-6471 and Obesity

gw-6471 has been researched along with Obesity* in 3 studies

Other Studies

3 other study(ies) available for gw-6471 and Obesity

ArticleYear
The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells.
    Journal of ethnopharmacology, 2017, Jan-04, Volume: 195

    Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation.. The effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.. Administration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells.. These results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases.

    Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Biomarkers; Cytokines; Disease Models, Animal; Fenofibrate; Gene Expression Regulation, Enzymologic; Hep G2 Cells; Hepatitis; Hepatocytes; Humans; Hypolipidemic Agents; Inflammation Mediators; Lipids; Lipogenesis; Liver; Male; Mice; Non-alcoholic Fatty Liver Disease; Obesity; Oxazoles; Plant Extracts; PPAR alpha; Rats, Inbred OLETF; RNA, Messenger; Transfection; Tyrosine

2017
Herbal composition Gambigyeongsinhwan (4) from Curcuma longa, Alnus japonica, and Massa Medicata Fermentata inhibits lipid accumulation in 3T3-L1 cells and regulates obesity in Otsuka Long-Evans Tokushima Fatty rats.
    Journal of ethnopharmacology, 2015, Aug-02, Volume: 171

    Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata.. The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red O staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.. GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPARγ, aP2, and C/EBPα) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARα target genes. GGH(4) and the individual components also increased PPARα reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARα target genes in OLETF rats.. These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARα activation.

    Topics: 3T3-L1 Cells; Alnus; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Proteins; Curcuma; Drugs, Chinese Herbal; Fatty Acid-Binding Proteins; Lipid Metabolism; Male; Medicine, Korean Traditional; Mice; Obesity; Oxazoles; Phytotherapy; Plant Extracts; Plant Preparations; PPAR alpha; PPAR gamma; Rats, Inbred OLETF; RNA, Messenger; Triglycerides; Tyrosine; Weight Gain

2015
Leptin induces hypertrophy through activating the peroxisome proliferator-activated receptor α pathway in cultured neonatal rat cardiomyocytes.
    Clinical and experimental pharmacology & physiology, 2010, Volume: 37, Issue:11

    1. Our previous study has shown that leptin induces cardiomyocyte hypertrophy; however, the mechanisms are poorly understood. Recent studies have shown that peroxisome proliferator-activated receptor α (PPARα) activation might be responsible for pathological remodeling and severe cardiomyopathy. Leptin, as an endogenous activator of PPARα, regulates energy metabolism through activating PPARα in many cells. Therefore, we hypothesized that leptin induces cardiomyocyte hypertrophy through activating the cardiac PPARα pathway. 2. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of PPARα on hypertrophy. The selective PPARα antagonist GW6471 concentration-dependently decreased atrial natriuretic factor mRNA expression by 23%, 36%, 44% and 59%, and significantly decreased total RNA levels, protein synthesis and cell surface areas, all of which were elevated by 72h of leptin treatment. The augmentation of reactive oxygen species levels in leptin treated cardiomyocytes was reversed by 0.1-10μmol/L GW6471 (40%, 52% and 58%). After 24h of treatment, leptin concentration-dependently enhanced mRNA expression by 7%, 93%, 100% and 256%, and protein expression by 31.2%, 64.2%, 143% and 199%, and the activity of PPARα. Meanwhile, cardiomycytes receiving 72h of treatment with the PPARα agonist, fenofibrate, concentration-dependently increased total RNA levels, atrial natriuretic factor mRNA expression, protein synthesis and cell surface area. Treatment of fenofibrate for 4 h also elevated oxygen species levels in a concentration-dependent manner. 3. In conclusion, these findings show that leptin induces hypertrophy through the activation of the PPARα pathway in cultured neonatal rat cardiomyocytes.

    Topics: Animals; Animals, Newborn; Blotting, Western; Cardiomegaly; Cell Culture Techniques; Cell Enlargement; Cells, Cultured; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Leptin; Myocytes, Cardiac; Obesity; Oxazoles; PPAR alpha; Protein Binding; Rats; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Tyrosine

2010