Differential roles of FOXO transcription factors on insulin action in brown and white adipose tissue
Authors
Homan, Erica PBrandão, Bruna B
Softic, Samir
El Ouaamari, Abdelfattah
O'Neill, Brian T
Kulkarni, Rohit N
Kim, Jason K
Kahn, C Ronald
UMass Chan Affiliations
MedicineDocument Type
Journal ArticlePublication Date
2021-08-24
Metadata
Show full item recordAbstract
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/JCI143328Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51659PubMed ID
34428182ae974a485f413a2113503eed53cd6c53
10.1172/JCI143328