Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease
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Journal ArticlePublication Date
2016-04-11Keywords
LipodystrophyObesity
Rapamycin
Raptor
White Adipose Tissue (WAT)
mTORC1
Cellular and Molecular Physiology
Nutritional and Metabolic Diseases
Skin and Connective Tissue Diseases
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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. 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.Source
Mol Metab. 2016 Apr 11;5(6):422-32. doi: 10.1016/j.molmet.2016.04.001. eCollection 2016. Link to article on publisher's site
DOI
10.1016/j.molmet.2016.04.001Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40017PubMed ID
27257602Related Resources
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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/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.molmet.2016.04.001
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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/).