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Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation

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Title: Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation
Author(s): Qiang, Guifen; Kong, Hyerim W.; Xu, Shanshan; Phan, Hoai A.; Parlee, Sebastian D.; Burr, Aaron A.; Gil, Victoria; Pang, Jingbo; Hughes, Amy; Gu, Xuejiang; Fantuzzi, Giamila; MacDougald, Ormond A.; Liew, Chongwee
Subject(s): Brown adipose tissue Insulin signaling Lipodystrophy Marrow adipose tissue White adipose tissue
Abstract: Objective: Insulin signaling plays pivotal roles in the development and metabolism of many tissues and cell types. A previous study demonstrated that ablation of insulin receptor (IR) with aP2-Cre markedly reduced adipose tissues mass and protected mice from obesity. However, multiple studies have demonstrated widespread non-adipocyte recombination of floxed alleles in aP2-Cre mice. These findings underscore the need to re-evaluate the role of IR in adipocyte and systemic metabolism with a more adipose tissue-specific Cre mouse line. Methods: We generated and phenotyped a new adipose tissue-specific IR mouse model using the adipose tissue-specific Adipoq-Cre line. Results: Here we show that the Adipoq-Cre-mediated IR KO in mice leads to lipodystrophy and metabolic dysfunction, which is in stark contrast to the previous study. In contrast to white adipocytes, absence of insulin signaling does not affect development of marrow and brown adipocytes, but instead is required for lipid accumulation particularly for the marrow adipocytes. Lipodystrophic IR KO mice have profound insulin resistance, hyperglycemia, organomegaly, and impaired adipokine secretion. Conclusions: Our results demonstrate differential roles for insulin signaling for white, brown, and marrow adipocyte development and metabolic regulation.
Issue Date: 2016-07-01
Publisher: Elsevier
Citation Info: Qiang, Guifen, Hyerim Whang Kong, Shanshan Xu, Hoai An Pham, Sebastian D. Parlee, Aaron A. Burr, Victoria Gil et al. "Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation." Molecular Metabolism (2016). DOI: 10.1016/j.molmet.2016.05.005
Type: Article
Description: This is a copy of an article published in the Molecular Metabolism. © 2016 The Author(s). http://dx.doi.org/10.1016/j.molmet.2016.05.005
URI: http://hdl.handle.net/10027/21166
Date Available in INDIGO: 2016-09-14
 

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