Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity_(accepted_version)
Accepteret manuskript, 2,25 MB, PDF-dokument
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Nature Metabolism |
Vol/bind | 1 |
Udgave nummer | 1 |
Sider (fra-til) | 133-146 |
Antal sider | 14 |
ISSN | 2522-5812 |
Status | Udgivet - 2019 |
Bibliografisk note
CURIS 2019 NEXS 013
- Det Natur- og Biovidenskabelige Fakultet
Forskningsområder
Links
- https://www.nature.com/articles/s42255-018-0007-6
Forlagets udgivne version
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
Ingen data tilgængelig
ID: 209516937