Journal article
Differential roles of FOXO transcription factors on insulin action in brown and white adipose tissue
The Journal of clinical investigation, Vol.131(19), pp.1-16
10/01/2021
DOI: 10.1172/JCI143328
PMCID: PMC8483763
PMID: 34428182
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.
Details
- Title: Subtitle
- Differential roles of FOXO transcription factors on insulin action in brown and white adipose tissue
- Creators
- Erica P Homan - Northeastern UniversityBruna B Brandão - Joslin Diabetes CenterSamir Softic - University of KentuckyAbdelfattah El Ouaamari - Joslin Diabetes CenterBrian T O'Neill - University of IowaRohit N Kulkarni - Joslin Diabetes CenterJason K Kim - University of Massachusetts Chan Medical SchoolC Ronald Kahn - Joslin Diabetes Center
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.131(19), pp.1-16
- DOI
- 10.1172/JCI143328
- PMID
- 34428182
- PMCID
- PMC8483763
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- R01 DK031036 / NIDDK NIH HHS R01 DK067536 / NIDDK NIH HHS P30 DK036836 / NIDDK NIH HHS P30 DK020541 / NIDDK NIH HHS R01 DK128429 / NIDDK NIH HHS T32 DK007260 / NIDDK NIH HHS R01 DK082659 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS R01 DK103215 / NIDDK NIH HHS
- Language
- English
- Date published
- 10/01/2021
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359861302771
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