Title
Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism
UMMS Affiliation
Program in Molecular Medicine; UMass Metabolic Network
Publication Date
2016-04-21
Document Type
Article
Disciplines
Endocrinology | Endocrinology, Diabetes, and Metabolism | Genetics and Genomics
Abstract
Adipose tissue de novo lipogenesis (DNL) positively influences insulin sensitivity, is reduced in obesity, and predicts insulin resistance. Therefore, elucidating mechanisms controlling adipose tissue DNL could lead to therapies for type 2 diabetes. Here, we report that mechanistic target of rapamycin complex 2 (mTORC2) functions in white adipose tissue (WAT) to control expression of the lipogenic transcription factor ChREBPbeta. Conditionally deleting the essential mTORC2 subunit Rictor in mature adipocytes decreases ChREBPbeta expression, which reduces DNL in WAT, and impairs hepatic insulin sensitivity. Mechanistically, Rictor/mTORC2 promotes ChREBPbeta expression in part by controlling glucose uptake, but without impairing pan-AKT signalling. High-fat diet also rapidly decreases adipose tissue ChREBPbeta expression and insulin sensitivity in wild-type mice, and does not further exacerbate insulin resistance in adipose tissue Rictor knockout mice, implicating adipose tissue DNL as an early target in diet-induced insulin resistance. These data suggest mTORC2 functions in WAT as part of an extra-hepatic nutrient-sensing mechanism to control glucose homeostasis.
Rights and Permissions
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
DOI of Published Version
10.1038/ncomms11365
Source
Nat Commun. 2016 Apr 21;7:11365. doi: 10.1038/ncomms11365. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
27098609
Repository Citation
Tang Y, Wallace M, Sanchez-Gurmaches J, Hsiao W, Li H, Lee PL, Vernia S, Metallo CM, Guertin DA. (2016). Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism. Open Access Publications by UMMS Authors. https://doi.org/10.1038/ncomms11365. Retrieved from https://escholarship.umassmed.edu/oapubs/2858
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Endocrinology Commons, Endocrinology, Diabetes, and Metabolism Commons, Genetics and Genomics Commons