Program in Molecular Medicine; UMass Metabolic Network
Endocrinology | Endocrinology, Diabetes, and Metabolism | Genetics and Genomics
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.
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DOI of Published Version
Nat Commun. 2016 Apr 21;7:11365. doi: 10.1038/ncomms11365. Link to article on publisher's site
Tang, Yuefeng; Wallace, Martina; Sanchez-Gurmaches, Joan; Hsiao, Wen-Yu; Li, Huawei; Lee, Peter L.; Vernia, Santiago; Metallo, Christian M.; and Guertin, David A., "Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism" (2016). Open Access Articles. 2858.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.