ChREBP Dotaz Zobrazit nápovědu
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.
- Klíčová slova
- ChREBP, ELOVL Fatty Acid Elongase 6, ELOVL6 Expression, Hormone-sensitive Lipase, Insulin Signaling,
- MeSH
- biologické markery MeSH
- elongasy mastných kyselin genetika metabolismus MeSH
- exprese genu MeSH
- fluidita membrány genetika MeSH
- glukosa metabolismus MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence * genetika MeSH
- mapování interakce mezi proteiny MeSH
- mapy interakcí proteinů MeSH
- myši transgenní MeSH
- myši MeSH
- signální transdukce MeSH
- sterolesterasa metabolismus MeSH
- transkripční faktory BHLH-Zip metabolismus MeSH
- tuková tkáň metabolismus MeSH
- tukové buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- elongasy mastných kyselin MeSH
- Elovl6 protein, mouse MeSH Prohlížeč
- glukosa MeSH
- inzulin MeSH
- Mlxipl protein, mouse MeSH Prohlížeč
- sterolesterasa MeSH
- transkripční faktory BHLH-Zip MeSH
Termites are among the few animals that themselves can digest the most abundant organic polymer, cellulose, into glucose. In mice and Drosophila, glucose can activate genes via the transcription factor carbohydrate-responsive element-binding protein (ChREBP) to induce glucose utilization and de novo lipogenesis. Here, we identify a termite orthologue of ChREBP and its downstream lipogenic targets, including acetyl-CoA carboxylase and fatty acid synthase. We show that all of these genes, including ChREBP, are upregulated in mature queens compared with kings, sterile workers and soldiers in eight different termite species. ChREBP is expressed in several tissues, including ovaries and fat bodies, and increases in expression in totipotent workers during their differentiation into neotenic mature queens. We further show that ChREBP is regulated by a carbohydrate diet in termite queens. Suppression of the lipogenic pathway by a pharmacological agent in queens elicits the same behavioural alterations in sterile workers as observed in queenless colonies, supporting that the ChREBP pathway partakes in the biosynthesis of semiochemicals that convey the signal of the presence of a fertile queen. Our results highlight ChREBP as a likely key factor for the regulation and signalling of queen fertility.
- Klíčová slova
- carbohydrate-responsive element-binding protein, lipogenesis, phenotypic plasticity, reproduction, social insects, transcription factor,
- MeSH
- fertilita MeSH
- fylogeneze MeSH
- glukosa metabolismus MeSH
- hmyzí proteiny metabolismus MeSH
- Isoptera klasifikace fyziologie MeSH
- lipogeneze MeSH
- mapy interakcí proteinů MeSH
- signální transdukce MeSH
- tkáňová distribuce MeSH
- transkripční faktory metabolismus MeSH
- upregulace * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glukosa MeSH
- hmyzí proteiny MeSH
- transkripční faktory MeSH