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Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
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Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

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

Partha Chakrabarti1, Ju Youn Kim, Maneet Singh

  • 1Boston University School of Medicine, Boston, Massachusetts, USA. pc1@csiriicb.in

Molecular and Cellular Biology
|July 17, 2013
PubMed

Insights

Insulin inhibits fat breakdown by reducing adipose triglyceride lipase (ATGL) transcription. A conserved mTORC1-Egr1 pathway mediates this effect, revealing a key mechanism for insulin

Area of Science:

  • Molecular biology
  • Cell biology
  • Metabolic regulation

Background:

  • Insulin's role in inhibiting lipolysis (fat breakdown) in adipocytes is crucial for triglyceride storage.
  • Previous studies identified the mTORC1 pathway's involvement in reducing adipose triglyceride lipase (ATGL) transcription, but the precise mechanism was unclear.

Purpose of the Study:

  • To identify the transcription factor mediating the effect of Tor1 on ATGL ortholog expression in yeast.
  • To elucidate the molecular mechanism by which insulin inhibits lipolysis in mammalian cells.

Main Methods:

  • Genetic screen in Saccharomyces cerevisiae to identify transcription factors.
  • In vitro assays to assess ATGL promoter activity.
  • Experiments using cultured adipocytes and animal models (high-fat diet).

Main Results:

  • A yeast transcription factor, Msn4p, was identified as mediating Tor1's effect on ATGL ortholog expression.
  • Msn4p homologues in mammals include early growth response transcription factors, such as Egr1.
  • Egr1 is induced by insulin and nutrients, directly inhibits ATGL promoter activity, and reduces ATGL expression in adipocytes.
  • High-fat diet increases mTORC1 activity and Egr1 expression while decreasing ATGL levels in epididymal fat.

Conclusions:

  • The mTORC1-Egr1-ATGL regulatory pathway is evolutionarily conserved.
  • This pathway is a significant component of insulin's antilipolytic effect in mammals.
  • Understanding this pathway offers insights into metabolic regulation and triglyceride storage.

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