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Hidden variant of ChREBP in fat links lipogenesis to insulin sensitivity
- Source :
- Cell Metab, Cell Metab, 2012, 15 (6), pp.795-7. 〈10.1016/j.cmet.2012.05.007〉, Nature, Cell Metab, 2012, 15 (6), pp.795-7. ⟨10.1016/j.cmet.2012.05.007⟩
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- Summary The prevalence of obesity and type 2-diabetes is increasing worldwide and threatens to shorten lifespan. Impaired insulin action in peripheral tissues is a major pathogenic factor. Insulin stimulates glucose uptake in adipose tissue through the Glut4-glucose transporter and alterations in adipose-Glut4 expression or function regulate systemic insulin sensitivity. Downregulation of adipose tissue-Glut4 occurs early in diabetes development. Here we report that adipose tissue-Glut4 regulates the expression of carbohydrate responsive-element binding protein (ChREBP), a transcriptional regulator of lipogenic and glycolytic genes. Furthermore, adipose-ChREBP is a major determinant of adipose tissue fatty acid synthesis and systemic insulin sensitivity. We discovered a new mechanism for glucose-regulation of ChREBP: Glucose-mediated activation of the canonical ChREBP isoform (ChREBPα) induces expression of a novel, potent isoform (ChREBPβ) that is transcribed from an alternative promoter. ChREBPβ expression in human adipose tissue predicts insulin sensitivity indicating that it may be an effective target for treating diabetes.
- Subjects :
- Gene isoform
medicine.medical_specialty
Physiology
030209 endocrinology & metabolism
White adipose tissue
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Carbohydrate-responsive element-binding protein
Molecular Biology
Transcription factor
030304 developmental biology
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
0303 health sciences
Mechanism (biology)
Chemistry
Glucose transporter
Insulin sensitivity
Cell Biology
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
[ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
3. Good health
Endocrinology
Lipogenesis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Metab, Cell Metab, 2012, 15 (6), pp.795-7. 〈10.1016/j.cmet.2012.05.007〉, Nature, Cell Metab, 2012, 15 (6), pp.795-7. ⟨10.1016/j.cmet.2012.05.007⟩
- Accession number :
- edsair.doi.dedup.....0d360e25ae5c3d6add3336757fda1ec9