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PPARγ mice showed more severe adipocyte hypertrophy, insulin resistance, and hepatic steatosis than wild type mice when fed with high-fat diet. These phenotypes were ameliorated after the transcription activity of PPARγ was restored by rosiglitazone, a PPARγ agonist. The current report presents a novel mouse model for investigating the role of PPARγ transcription in physiological functions. The data demonstrate that the transcriptional activity plays an indispensable role for PPARγ in metabolic regulation. The current report presents a n