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dc.contributor.authorTang, Yuefeng
dc.contributor.authorWallace, Martina
dc.contributor.authorSanchez-Gurmaches, Joan
dc.contributor.authorHsiao, Wen-Yu
dc.contributor.authorLi, Huawei
dc.contributor.authorLee, Peter L.
dc.contributor.authorVernia, Santiago
dc.contributor.authorMetallo, Christian M.
dc.contributor.authorGuertin, David A.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:42:15Z
dc.date.available2022-08-23T16:42:15Z
dc.date.issued2016-04-21
dc.date.submitted2016-08-16
dc.identifier.citationNat Commun. 2016 Apr 21;7:11365. doi: 10.1038/ncomms11365. <a href="http://dx.doi.org/10.1038/ncomms11365">Link to article on publisher's site</a>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/ncomms11365
dc.identifier.pmid27098609
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40053
dc.description.abstractAdipose 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27098609&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsThis 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/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectEndocrinology
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectGenetics and Genomics
dc.titleAdipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume7
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3863&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2858
dc.identifier.contextkey8985409
refterms.dateFOA2022-08-23T16:42:15Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2858
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages11365


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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/
Except where otherwise noted, this item's license is described as 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/