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A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.

Publication ,  Journal Article
Herman, MA; Peroni, OD; Villoria, J; Schön, MR; Abumrad, NA; Blüher, M; Klein, S; Kahn, BB
Published in: Nature
April 19, 2012

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 (also known as SLC2A4) glucose transporter, and alterations in adipose tissue GLUT4 expression or function regulate systemic insulin sensitivity. Downregulation of human and mouse 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; also known as MLXIPL), 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 find a new mechanism for glucose regulation of ChREBP: glucose-mediated activation of the canonical ChREBP isoform (ChREBP-α) induces expression of a novel, potent isoform (ChREBP-β) that is transcribed from an alternative promoter. ChREBP-β expression in human adipose tissue predicts insulin sensitivity, indicating that it may be an effective target for treating diabetes.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

April 19, 2012

Volume

484

Issue

7394

Start / End Page

333 / 338

Location

England

Related Subject Headings

  • Transcription Factors
  • RNA, Messenger
  • Protein Isoforms
  • Promoter Regions, Genetic
  • Obesity
  • Nuclear Proteins
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Herman, M. A., Peroni, O. D., Villoria, J., Schön, M. R., Abumrad, N. A., Blüher, M., … Kahn, B. B. (2012). A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature, 484(7394), 333–338. https://doi.org/10.1038/nature10986
Herman, Mark A., Odile D. Peroni, Jorge Villoria, Michael R. Schön, Nada A. Abumrad, Matthias Blüher, Samuel Klein, and Barbara B. Kahn. “A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.Nature 484, no. 7394 (April 19, 2012): 333–38. https://doi.org/10.1038/nature10986.
Herman MA, Peroni OD, Villoria J, Schön MR, Abumrad NA, Blüher M, et al. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature. 2012 Apr 19;484(7394):333–8.
Herman, Mark A., et al. “A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.Nature, vol. 484, no. 7394, Apr. 2012, pp. 333–38. Pubmed, doi:10.1038/nature10986.
Herman MA, Peroni OD, Villoria J, Schön MR, Abumrad NA, Blüher M, Klein S, Kahn BB. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature. 2012 Apr 19;484(7394):333–338.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

April 19, 2012

Volume

484

Issue

7394

Start / End Page

333 / 338

Location

England

Related Subject Headings

  • Transcription Factors
  • RNA, Messenger
  • Protein Isoforms
  • Promoter Regions, Genetic
  • Obesity
  • Nuclear Proteins
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice
  • Male