Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Nature Metabolism Year : 2019

Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity

Fadila Benhamed
Sandra Guilmeau
  • Function : Author
Thierry Sulpice
  • Function : Author
Catherine Postic
  • Function : Author

Abstract

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency–mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBPα impairs ChREBPα translocation into the nucleus and induction of ChREBPβ, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL–ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity
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Dates and versions

inserm-02150261 , version 1 (07-06-2019)

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Pauline Morigny, Marianne Houssier, Aline Mairal, Claire Ghilain, Etienne Mouisel, et al.. Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity. Nature Metabolism, 2019, 1 (1), pp.133-146. ⟨10.1038/s42255-018-0007-6⟩. ⟨inserm-02150261⟩
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