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Peroxisome Proliferator‐Activated Receptorγ Agonist Rosiglitazone Increases Expression of Lipin‐1 in Adipocytes
Author(s) -
Kim Jina,
Han Dong Cho,
Kwon ByoungMog
Publication year - 2010
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.24.1_supplement.914.2
Subject(s) - rosiglitazone , adipogenesis , peroxisome proliferator activated receptor , phosphorylation , endocrinology , medicine , adipocyte , mapk/erk pathway , chemistry , kinase , agonist , small interfering rna , microbiology and biotechnology , peroxisome , receptor , 3t3 l1 , biology , transfection , biochemistry , adipose tissue , gene
We investigate the possibility that lipin‐1 inhibits the phosphorylation of extracellular‐signal regulated kinases 1 and 2 (ERK1/2) and peroxisome proliferators‐activated receptorγ (PPARγ). Rosiglitazone (RGZ) is well known PPARγ agonist using for the type 2 diabetes mellitus therapy with side effect such as inducing obesity. RGZ enhances 3T3‐L1 adipocyte differentiation and lipin‐1 expression. Lipin‐1 is a novel family of Mg2+‐dependent phosphatidate phosphatases (PAP1 enzymes) that play key roles in fat metabolism and lipid biosynthesis. Phosphorylation of ERK1/2 and PPARγ are suppressed by RGZ in 3T3‐L1 cells. Phospho‐ERK1/2 is translocated into the nucleus and induces phosphorylation of PPARγ, which decreases PPARγ transcriptional activity and then inhibits adipocyte differentiation. In RGZ‐treated 3T3‐L1 preadipocyte, transfection of lipin‐1 small interfering RNA increased phosphorylation of ERK1/2 and PPARγ. These results suggest that RGZ induced adipogenesis through the expression of lipin‐1 to lead inhibition of ERK pathway and transcriptional activation of PPARγ. We conclude that rosiglitazone directly increases lipin‐1 expression, thereby inhibiting phosphorylation of ERK and PPARγ in adipocytes.