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Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway

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Title Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway
 
Creator Chakrabarti, Partha
Kim, Ju Youn
Singh, Maneet
Kim, Jessica
Kumbrink, Joerg
Wu, Yuanyuan
Lee, Mi-Jeong
Kirsch, Kathrin H.
Fried, Susan K.
Kandror, Konstantin V
Shin, Yu-Kyong
 
Subject Cell Biology & Physiology
 
Description One of the basic functions of insulin in the body is to inhibit lipolysis in adipocytes. Recently, we have found that insulin inhibits lipolysis and promotes triglyceride storage by decreasing transcription of adipose triglyceride lipase via the mTORC1-mediated pathway (P. Chakrabarti et al., Diabetes 59:775–781, 2010), although the mechanism of this effect remained unknown. Here, we used a genetic screen in Saccharomyces cerevisiae in order to identify a transcription factor that mediates the effect of Tor1 on
the expression of the ATGL ortholog in yeast. This factor, Msn4p, has homologues in mammalian cells that form a family of early growth response transcription factors. One member of the family, Egr1, is induced by insulin and nutrients and directly inhibits activity of the ATGL promoter in vitro and expression of ATGL in cultured adipocytes. Feeding animals a high-fat diet increases the activity of mTORC1 and the expression of Egr1 while decreasing ATGL levels in epididymal fat. We suggest that the evolutionarily
conserved mTORC1-Egr1-ATGL regulatory pathway represents an important component of the antilipolytic effect of
insulin in the mammalian organism.
 
Publisher American Society for Microbiology
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2435/1/MOLECULAR_AND_CELLULAR_BIOLOGY__Volume__33____Issue__18____Pages__3659%2D3666;2013.pdf
Chakrabarti, Partha and Kim, Ju Youn and Singh, Maneet and Kim, Jessica and Kumbrink, Joerg and Wu, Yuanyuan and Lee, Mi-Jeong and Kirsch, Kathrin H. and Fried, Susan K. and Kandror, Konstantin V and Shin, Yu-Kyong (2013) Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway. Molecular and Cellular Biology, 33 (18). pp. 3659-3666.
 
Relation http://dx.doi.org/10.1128/MCB.01584-12
http://www.eprints.iicb.res.in/2435/