Insulin inhibits lipolysis in adipocytes via the evolutionarily conserved mTORC1-Egr1-ATGL-mediated pathway

Partha Chakrabarti, Ju Youn Kim, Maneet Singh, Yu Kyong Shin, Jessica Kim, Joerg Kumbrink, Yuanyuan Wu, Mi Jeong Lee, Kathrin H. Kirsch, Susan K. Fried, Konstantin V. Kandror

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3659-3666
Number of pages8
JournalMolecular and Cellular Biology
Volume33
Issue number18
DOIs
StatePublished - 2013
Externally publishedYes

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