gw-501516 and Non-alcoholic-Fatty-Liver-Disease

gw-501516 has been researched along with Non-alcoholic-Fatty-Liver-Disease* in 4 studies

Reviews

2 review(s) available for gw-501516 and Non-alcoholic-Fatty-Liver-Disease

ArticleYear
New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease.
    Expert opinion on pharmacotherapy, 2014, Volume: 15, Issue:4

    Novel peroxisome proliferator-activated receptor (PPAR) modulators (selective PPAR modulators [SPPARMs]) and dual PPAR agonists may have an important role in the treatment of cardiometabolic disorders owing to lipid-modifying, insulin-sensitizing and anti-inflammatory effects.. This review summarizes the efficacy of new PPAR agonists and SPPARMs that are under development for the treatment of atherogenic dyslipidemia and non-alcoholic fatty liver disease (NAFLD).. ABT-335 is a new formulation of fenofibrate that has been approved for concomitant use with statins. K-877, a SPPARM-α with encouraging preliminary results in modulating atherogenic dyslipidemia, and INT131, a SPPARM-γ with predominantly insulin-sensitizing actions, may also have favorable lipid-modifying effects. Although the development of dual PPAR-α/γ agonists (glitazars) and the SPPARM-δ GW501516 has been abandoned because of safety issues, another SPPARM-δ (MBX-8025) and a dual PPAR-α/δ agonist (GFT-505) have shown promising efficacy in decreasing plasma triglyceride and increasing high-density lipoprotein cholesterol concentrations, as well as improving insulin sensitivity and liver function. The beneficial effects of GFT-505 are complemented by preclinical findings that indicate reduction of hepatic fat accumulation, inflammation and fibrosis, making it a promising candidate for the treatment of NAFLD/nonalcoholic steatohepatitis (NASH). Long-term trials are required to test the efficacy and safety of these new PPAR agonists in reducing cardiovascular outcomes and treating NAFLD/NASH.

    Topics: Acetates; Animals; Atherosclerosis; Chalcones; Cholesterol, HDL; Dyslipidemias; Fatty Liver; Fenofibrate; Humans; Insulin Resistance; Lipoproteins, HDL; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Propionates; Quinolines; Sulfonamides; Thiazoles; Triazoles; Triglycerides

2014
Roles of PPARs in NAFLD: potential therapeutic targets.
    Biochimica et biophysica acta, 2012, Volume: 1821, Issue:5

    Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increasing prevalence due to the obesity epidemic. Hence, NAFLD represents a rising threat to public health. Currently, no effective treatments are available to treat NAFLD and its complications such as cirrhosis and liver cancer. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors which regulate lipid and glucose metabolism as well as inflammation. Here we review recent findings on the pathophysiological role of PPARs in the different stages of NAFLD, from steatosis development to steatohepatitis and fibrosis, as well as the preclinical and clinical evidence for potential therapeutical use of PPAR agonists in the treatment of NAFLD. PPARs play a role in modulating hepatic triglyceride accumulation, a hallmark of the development of NAFLD. Moreover, PPARs may also influence the evolution of reversible steatosis toward irreversible, more advanced lesions. Presently, large controlled trials of long duration are needed to assess the long-term clinical benefits of PPAR agonists in humans. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

    Topics: Clinical Trials as Topic; Fatty Liver; Gene Expression; Humans; Inflammation; Liver; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Thiazoles; Triglycerides

2012

Other Studies

2 other study(ies) available for gw-501516 and Non-alcoholic-Fatty-Liver-Disease

ArticleYear
Treatment with PPARδ agonist alleviates non-alcoholic fatty liver disease by modulating glucose and fatty acid metabolic enzymes in a rat model.
    International journal of molecular medicine, 2015, Volume: 36, Issue:3

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition which is associated with certain features of metabolic syndrome and insulin resistance. Peroxisome proliferator‑activated receptor (PPAR)δ is an important regulator of energy metabolism and insulin resistance in diabetes. However, the function of PPARδ in NAFLD has not yet been fully elucidated. In the present study, in order to explore the function of PPARδ in NAFLD, we created a rat model of NALFD induced by a high-fat diet (HFD) and treated the rats with GW501516, a PPARδ agonist. We found that the lipid levels decreased, and hepatocellular ballooning and inflammatory cell infiltration were also significantly decreased following treatment of the rats with GW501516 compared to the untreated rats. Treatment with GW501516 also significantly decreased the homeostasis model assessment of insulin resistance (HOMA-IR) index, as well as the low‑density lipoprotein (LDL) levels. In addition, treatment with GW501516 increased the levels of insulin‑like growth factor‑1 (IGF-1) and high‑density lipoprotein (HDL) compared to the HFD group. Furthermore, the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) in the HFD group were all restored to the normal control levels following treatment with GW501516. RT‑qPCR and immunohistochemical staining revealed that the expression levels of sterol regulatory element binding protein‑1c (SREBP‑1c) and glucose transporter 2 (GLUT‑2) were both restored to normal control levels following treatment with GW501516. Also, the levels of enzymes related to lipid metabolism were increased following treatment with GW501516. In conclusion, our findings demonstrate that treatment with GW501516 alleviates NAFLD by modulating glucose and fatty acid metabolism.

    Topics: Animals; Fatty Acids; Gene Expression Regulation; Glucose; Glucose Transporter Type 2; Liver; Male; Non-alcoholic Fatty Liver Disease; PPAR delta; Rats; Rats, Sprague-Dawley; Sterol Regulatory Element Binding Protein 1; Thiazoles

2015
Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease.
    World journal of gastroenterology, 2015, Dec-07, Volume: 21, Issue:45

    To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models.. Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW.. HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.. PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.

    Topics: Animals; Anti-Inflammatory Agents; Blood Glucose; Cytoprotection; Diet, High-Fat; Disease Models, Animal; Gene Expression Regulation; Hep G2 Cells; Hepatocytes; Humans; Inflammasomes; Inflammation Mediators; Lipopolysaccharides; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Palmitic Acid; PPAR delta; Signal Transduction; Thiazoles; Time Factors

2015