TonEBP suppresses adipogenesis and insulin sensitivity by blocking epigenetic transition of PPARγ2

• Published in: Scientific reports Vol. 5; no. 1; p. 10937
• Main Authors: Lee, Jun Ho, Lee, Hwan Hee, Ye, Byeong Jin, Lee-Kwon, Whaseon, Choi, Soo Youn, Kwon, Hyug Moo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-06-2015; Nature Publishing Group
• Subjects: 38/1; 38/109; 3T3-L1 Cells; 45/15; 45/22; 631/337/100/102; 631/337/100/2285; 631/80/304; 64/60; Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis - genetics; Adiponectin - genetics; Adiponectin - metabolism; Animals; Cell Differentiation - genetics; Chromatin - metabolism; Cytokines - genetics; Cytokines - metabolism; Down-Regulation; Epigenesis, Genetic; Gene Expression Regulation; Gene Knockdown Techniques; Histones - metabolism; Humanities and Social Sciences; Inflammation Mediators - metabolism; Insulin Resistance - genetics; Methylation; Mice; multidisciplinary; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; PPAR gamma - genetics; Promoter Regions, Genetic; Protein Binding; Science; Signal Transduction; Transcriptional Activation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep10937

TonEBP is a key transcription factor in cellular adaptation to hypertonic stress and also in macrophage activation. Since TonEBP is involved in inflammatory diseases such as rheumatoid arthritis and atherosclerosis, we asked whether TonEBP played a role in adipogenesis and insulin resistance. Here we report that TonEBP suppresses adipogenesis and insulin signaling by inhibiting expression of the key transcription factor PPARγ2. TonEBP binds to the PPARγ2 promoter and blocks the epigenetic transition of the locus which is required for the activation of the promoter. When TonEBP expression is reduced, the epigenetic transition and PPARγ2 expression are markedly increased leading to enhanced adipogenesis and insulin response while inflammation is reduced. Thus, TonEBP is an independent determinant of adipose insulin sensitivity and inflammation. TonEBP is an attractive therapeutic target for insulin resistance in lieu of PPARγ agonists.