[PPARgamma antagonist as a potential drug for the treatment of obesity and diabetes].
PPARgamma is a molecular target of thiazolidinedione class of antidiabetic drugs. Although activation of PPARgamma by thiazolidinedione improves insulin resistance in obese subjects, PPARgamma heterozygous knockout mice were resistant to a high-fat diet induced obesity and insulin resistance, suggesting that a moderate reduction of PPARgamma activity could be beneficial for the treatment of obesity and insulin resistance. This hypothesis was supported by genetic evidences consistently showing that the common Pro12Ala variant of PPARgamma2, which causes a moderate reduction in transcriptional activity and adipogenic potential, has been associated with reduced weight gain and improved insulin sensitivity. We here review PPARgamma antagonism as a potential remedy for obesity and diabetes.
Waki
Hironori
H
Department of Metabolic Diseases, Graduate School of Medicine, the University of Tokyo.
Yamauchi
Toshimasa
T
Kadowaki
Takashi
T
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D009765:Obesity / Q000188:drug therapy*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*
D001565:Benzoates; D001713:Biphenyl Compounds; D047495:PPAR gamma; C438269:diazepinylbenzoic acid