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    Differential roles of FOXO transcription factors on insulin action in brown and white adipose tissue

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    Authors
    Homan, Erica P
    Brandão, Bruna B
    Softic, Samir
    El Ouaamari, Abdelfattah
    O'Neill, Brian T
    Kulkarni, Rohit N
    Kim, Jason K
    Kahn, C Ronald
    UMass Chan Affiliations
    Medicine
    Document Type
    Journal Article
    Publication Date
    2021-08-24
    Keywords
    Adipose tissue
    Endocrinology
    Insulin signaling
    Metabolism
    Transcription
    
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    Link to Full Text
    https://doi.org/10.1172/jci143328
    Abstract
    Insulin and IGF-1 are essential for adipocyte differentiation and function. Mice lacking insulin and IGF-1 receptors in fat (FIGIR-KO, fat-specific IGF-1 receptor and insulin receptor-KO) exhibit complete loss of white and brown adipose tissue (WAT and BAT), glucose intolerance, insulin resistance, hepatosteatosis, and cold intolerance. To determine the role of FOXO transcription factors in the altered adipose phenotype, we generated FIGIR-KO mice with fat-specific KO of fat-expressed Foxos [Foxo1, Foxo3, Foxo4] (F-Quint-KO). Unlike FIGIR-KO mice, F-Quint-KO mice had normal BAT, glucose tolerance, insulin-regulated hepatic glucose production, and cold tolerance. However, loss of FOXOs only partially rescued subcutaneous WAT and hepatosteatosis, did not rescue perigonadal WAT or systemic insulin resistance, and led to even more marked hyperinsulinemia. Thus, FOXOs play different roles in insulin/IGF-1 action in different adipose depots, being most important in BAT, followed by subcutaneous WAT and then by visceral WAT. Disruption of FOXOs in fat also led to a reversal of insulin resistance in liver, but not in skeletal muscle, and an exacerbation of hyperinsulinemia. Thus, adipose FOXOs play a unique role in regulating crosstalk between adipose depots, liver, and β cells.
    Source
    Homan EP, Brandão BB, Softic S, El Ouaamari A, O'Neill BT, Kulkarni RN, Kim JK, Kahn CR. Differential roles of FOXO transcription factors on insulin action in brown and white adipose tissue. J Clin Invest. 2021 Oct 1;131(19):e143328. doi: 10.1172/JCI143328. PMID: 34428182; PMCID: PMC8483763.
    DOI
    10.1172/JCI143328
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/51659
    PubMed ID
    34428182
    ae974a485f413a2113503eed53cd6c53
    10.1172/JCI143328
    Scopus Count
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    UMass Chan Faculty and Researcher Publications

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