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A Novel Peroxisome Proliferator‐activated Receptor γ Agonist, KR‐62776, does not Trigger the Gene Expression of PPAR γ 2 Gene Isoform
Author(s) -
Kim Jung Min,
Lee SuKyung,
Cheon Hyae Gyeong,
Kim Sung Soo,
Son KwangHee,
Yeom YoungIl,
Han DongCho,
Kwon ByoungMog
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a938-a
Subject(s) - adipocyte , peroxisome proliferator activated receptor , agonist , gene isoform , receptor , gene expression , chemistry , microbiology and biotechnology , in vitro , endocrinology , regulation of gene expression , cell culture , biology , medicine , gene , biochemistry , adipose tissue , genetics
PPAR γ agonists such as the TZDs are insulin sensitizers used in the treatment of type 2 diabetes. A novel ligand, KR‐62776, binds to PPAR γ in vitro and exhibits an antihyperglycemic activity in vivo, however, it competitively blocks TZD‐induced PPAR γ activation and adipocyte conversion in cell culture model as measured by Oil‐Red O staining. To elucidate the differences between the well‐known PPAR agonists and KR‐62776 in the regulation of adipocyte differentiation, gene expression profiles of five different agonists were investigated in 3T3‐L1, C3H/10T1/2, and HepG2. In the adipocytic cells, adipocyte genes were up‐regulated by TZDs, however, KR‐62776 did not activated. When the gene expression profiles of the HepG2 cells were examined after treatment of KR‐62776, RGZ, and Wy‐14643, KR‐62776 and RGZ showed most similar gene expression profiles, but not Wy‐14643. The use of the PPAR γ agonist KR‐62776 as a molecular tool in both adipocytes and animal models promises to be powerful approach for dissecting PPAR γ biology and the design of PPAR γ ligands to the prevention for side effects.