UMMS Affiliation

Program in Molecular Medicine; UMass Metabolic Network

Date

4-21-2016

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

Citation: Nat Commun. 2016 Apr 21;7:11365. doi: 10.1038/ncomms11365. Link to article on publisher's site

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

Related Resources

Link to Article in PubMed

Journal Title

Nature communications

PubMed ID

27098609

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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