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- W2015508853 abstract "Abstract LSN862 is a novel peroxisome proliferator-activated receptor (PPAR)α/γ dual agonist with a unique in vitro profile that shows improvements on glucose and lipid levels in rodent models of type 2 diabetes and dyslipidemia. Data from in vitro binding, cotransfection, and cofactor recruitment assays characterize LSN862 as a high-affinity PPARγ partial agonist with relatively less but significant PPARα agonist activity. Using these same assays, rosiglitazone was characterized as a high-affinity PPARγ full agonist with no PPARα activity. When administered to Zucker diabetic fatty rats, LSN862 displayed significant glucose and triglyceride lowering and a significantly greater increase in adiponectin levels compared with rosiglitazone. Expression of genes involved in metabolic pathways in the liver and in two fat depots from compound-treated Zucker diabetic fatty rats was evaluated. Only LSN862 significantly elevated mRNA levels of pyruvate dehydrogenase kinase isozyme 4 and bifunctional enzyme in the liver and lipoprotein lipase in both fat depots. In contrast, both LSN862 and rosiglitazone decreased phosphoenol pyruvate carboxykinase in the liver and increased malic enzyme mRNA levels in the fat. In addition, LSN862 was examined in a second rodent model of type 2 diabetes, db/db mice. In this study, LSN862 demonstrated statistically better antidiabetic efficacy compared with rosiglitazone with an equivalent side effect profile. LSN862, rosiglitazone, and fenofibrate were each evaluated in the humanized apoA1 transgenic mouse. At the highest dose administered, LSN862 and fenofibrate reduced very low-density lipoprotein cholesterol, whereas, rosiglitazone increased very low-density lipoprotein cholesterol. LSN862, fenofibrate, and rosiglitazone produced maximal increases in high-density lipoprotein cholesterol of 65, 54, and 30%, respectively. These findings show that PPARγ full agonist activity is not necessary to achieve potent and efficacious insulin-sensitizing benefits and demonstrate the therapeutic advantages of a PPARα/γ dual agonist." @default.
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- W2015508853 date "2005-06-01" @default.
- W2015508853 modified "2023-09-27" @default.
- W2015508853 title "A Peroxisome Proliferator-Activated Receptor α/γ Dual Agonist with a Unique in Vitro Profile and Potent Glucose and Lipid Effects in Rodent Models of Type 2 Diabetes and Dyslipidemia" @default.
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- W2015508853 cites W1513078811 @default.
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- W2015508853 cites W1587875569 @default.
- W2015508853 cites W193153926 @default.
- W2015508853 cites W1969437387 @default.
- W2015508853 cites W1969478165 @default.
- W2015508853 cites W1971082641 @default.
- W2015508853 cites W1974418613 @default.
- W2015508853 cites W1989951988 @default.
- W2015508853 cites W2010255414 @default.
- W2015508853 cites W2015279471 @default.
- W2015508853 cites W2015495335 @default.
- W2015508853 cites W2021760176 @default.
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- W2015508853 cites W2024326679 @default.
- W2015508853 cites W2027702484 @default.
- W2015508853 cites W2031898359 @default.
- W2015508853 cites W2033752591 @default.
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- W2015508853 cites W2045432341 @default.
- W2015508853 cites W2045639368 @default.
- W2015508853 cites W2046268728 @default.
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- W2015508853 cites W2096712675 @default.
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- W2015508853 cites W2114215010 @default.
- W2015508853 cites W2117219849 @default.
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- W2015508853 doi "https://doi.org/10.1210/me.2005-0015" @default.
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