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dc.contributor.authorLee, Peter L.
dc.contributor.authorTang, Yuefeng
dc.contributor.authorLi, Huawei
dc.contributor.authorGuertin, David A.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:42:05Z
dc.date.available2022-08-23T16:42:05Z
dc.date.issued2016-04-11
dc.date.submitted2016-08-16
dc.identifier.citation<p>Mol Metab. 2016 Apr 11;5(6):422-32. doi: 10.1016/j.molmet.2016.04.001. eCollection 2016. <a href="http://dx.doi.org/10.1016/j.molmet.2016.04.001">Link to article on publisher's site</a></p>
dc.identifier.issn2212-8778 (Linking)
dc.identifier.doi10.1016/j.molmet.2016.04.001
dc.identifier.pmid27257602
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40017
dc.description.abstractOBJECTIVE: Normal adipose tissue growth and function is critical to maintaining metabolic homeostasis and its excess (e.g. obesity) or absence (e.g. lipodystrophy) is associated with severe metabolic disease. The goal of this study was to understand the mechanisms maintaining healthy adipose tissue growth and function. METHODS: Adipose tissue senses and responds to systemic changes in growth factor and nutrient availability; in cells mTORC1 regulates metabolism in response to growth factors and nutrients. Thus, mTORC1 is poised to be a critical intracellular regulator of adipocyte metabolism. Here, we investigate the role of mTORC1 in mature adipocytes by generating and characterizing mice in which the Adiponectin-Cre driver is used to delete floxed alleles of Raptor, which encodes an essential regulatory subunit of mTORC1. RESULTS: Raptor (Adipoq-cre) mice have normal white adipose tissue (WAT) mass for the first few weeks of life, but soon thereafter develop lipodystrophy associated with hepatomegaly, hepatic steatosis, and insulin intolerance. Raptor (Adipoq-cre) mice are also resistant to becoming obese when consuming a high fat diet (HFD). Resistance to obesity does not appear to be due to increased energy expenditure, but rather from failed adipose tissue expansion resulting in severe hepatomegaly associated with hyperphagia and defective dietary lipid absorption. Deleting Raptor in WAT also decreases C/EBPalpha expression and the expression of its downstream target adiponectin, providing one possible mechanism of mTORC1 function in WAT. CONCLUSIONS: mTORC1 activity in mature adipocytes is essential for maintaining normal adipose tissue growth and its selective loss in mature adipocytes leads to a progressive lipodystrophy disorder and systemic metabolic disease that shares many of the hallmarks of human congenital generalized lipodystrophy.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27257602&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectLipodystrophy
dc.subjectObesity
dc.subjectRapamycin
dc.subjectRaptor
dc.subjectWhite Adipose Tissue (WAT)
dc.subjectmTORC1
dc.subjectCellular and Molecular Physiology
dc.subjectNutritional and Metabolic Diseases
dc.subjectSkin and Connective Tissue Diseases
dc.titleRaptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease
dc.typeJournal Article
dc.source.journaltitleMolecular metabolism
dc.source.volume5
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3829&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2824
dc.identifier.contextkey8985334
refterms.dateFOA2022-08-23T16:42:05Z
html.description.abstract<p>OBJECTIVE: Normal adipose tissue growth and function is critical to maintaining metabolic homeostasis and its excess (e.g. obesity) or absence (e.g. lipodystrophy) is associated with severe metabolic disease. The goal of this study was to understand the mechanisms maintaining healthy adipose tissue growth and function.</p> <p>METHODS: Adipose tissue senses and responds to systemic changes in growth factor and nutrient availability; in cells mTORC1 regulates metabolism in response to growth factors and nutrients. Thus, mTORC1 is poised to be a critical intracellular regulator of adipocyte metabolism. Here, we investigate the role of mTORC1 in mature adipocytes by generating and characterizing mice in which the Adiponectin-Cre driver is used to delete floxed alleles of Raptor, which encodes an essential regulatory subunit of mTORC1.</p> <p>RESULTS: Raptor (Adipoq-cre) mice have normal white adipose tissue (WAT) mass for the first few weeks of life, but soon thereafter develop lipodystrophy associated with hepatomegaly, hepatic steatosis, and insulin intolerance. Raptor (Adipoq-cre) mice are also resistant to becoming obese when consuming a high fat diet (HFD). Resistance to obesity does not appear to be due to increased energy expenditure, but rather from failed adipose tissue expansion resulting in severe hepatomegaly associated with hyperphagia and defective dietary lipid absorption. Deleting Raptor in WAT also decreases C/EBPalpha expression and the expression of its downstream target adiponectin, providing one possible mechanism of mTORC1 function in WAT.</p> <p>CONCLUSIONS: mTORC1 activity in mature adipocytes is essential for maintaining normal adipose tissue growth and its selective loss in mature adipocytes leads to a progressive lipodystrophy disorder and systemic metabolic disease that shares many of the hallmarks of human congenital generalized lipodystrophy.</p>
dc.identifier.submissionpathoapubs/2824
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages422-32


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Copyright © 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright © 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).