The PDK1-FoxO1 signaling in adipocytes controls systemic insulin sensitivity through the 5-lipoxygenase-leukotriene B
5-lipoxygenase
FoxO1
PDK1
insulin resistance
leukotriene B4
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
26 05 2020
26 05 2020
Historique:
pubmed:
13
5
2020
medline:
19
8
2020
entrez:
13
5
2020
Statut:
ppublish
Résumé
Although adipocytes are major targets of insulin, the influence of impaired insulin action in adipocytes on metabolic homeostasis remains unclear. We here show that adipocyte-specific PDK1 (3'-phosphoinositide-dependent kinase 1)-deficient (A-PDK1KO) mice manifest impaired metabolic actions of insulin in adipose tissue and reduction of adipose tissue mass. A-PDK1KO mice developed insulin resistance, glucose intolerance, and hepatic steatosis, and this phenotype was suppressed by additional ablation of FoxO1 specifically in adipocytes (A-PDK1/FoxO1KO mice) without an effect on adipose tissue mass. Neither circulating levels of adiponectin and leptin nor inflammatory markers in adipose tissue differed between A-PDK1KO and A-PDK1/FoxO1KO mice. Lipidomics and microarray analyses revealed that leukotriene B
Identifiants
pubmed: 32393635
pii: 1921015117
doi: 10.1073/pnas.1921015117
pmc: PMC7261087
doi:
Substances chimiques
Forkhead Box Protein O1
0
Foxo1 protein, mouse
0
Leukotriene B4
1HGW4DR56D
Arachidonate 5-Lipoxygenase
EC 1.13.11.34
3-Phosphoinositide-Dependent Protein Kinases
EC 2.7.11.1
Pdpk1 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11674-11684Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK063608
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK058282
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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