Fas activation in adipocytes impairs insulin-stimulated glucose uptake by reducing Akt.
Fas (CD95) belongs to the superfamily of the tumor necrosis factor (TNF) receptors. Besides its key role in apoptosis, Fas contributes to non-apoptotic pathways such as cell proliferation and inflammation. In 3T3-L1 adipocytes, activation of Fas by Fas ligand decreased insulin-stimulated glucose uptake, without affecting cell viability. This decrease in glucose uptake was accompanied by reduced protein expression and diminished phosphorylation of Akt. Similarly, insulin-stimulated glucose incorporation and protein levels of Akt were increased in isolated adipocytes from Fas deficient mice when compared to wild-type mice. In conclusion, Fas activation in adipocytes decreases Akt expression and thereby impairs insulin sensitivity.
Wueest
Stephan
S
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland.
Rapold
Reto A
RA
Schoenle
Eugen J
EJ
Konrad
Daniel
D
D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D053222:Fas Ligand Protein / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D007328:Insulin; D019014:fas Receptor; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose