title: Central FoxO3a and FoxO6 expression is down-regulated in obesity induced diabetes but not in aging.
abstract: BACKGROUND
  Recent data suggest that insulin-like growth factor (IGF)-1 resistance in neurons prolongs longevity. In C. elegans this effect is mediated via DAF-16 the ortholog of the mammalian FoxO transcription factors. 3 different FoxO transcription factors (FoxOs) are expressed in rodent CNS: FoxO1, FoxO3a and FoxO6.
  
  
  METHODS
  To define whether the different FoxOs are region-, sex- and age-specifically expressed, we analyzed FoxO mRNA levels in different brain regions from 6, 16, 60 and 100 weeks old mice using realtime-PCR. In addition, we fed mice a high fat diet (HFD) to experimentally induce obesity and diabetes and analyzed FoxO mRNA in the different brain regions.
  
  
  RESULTS
  Interestingly, FoxO1 was predominantly expressed in the hippocampus whereas FoxO3a was quantitatively the most abundant FoxO in the neocortex. During aging, FoxO1 expression peaked in all brain regions at 16 weeks and FoxO6 showed its highest expression at 60 weeks in the parietal and occipital cortex. In 6 weeks old mice FoxO6 expression was higher in male compared to female mice in the hippocampus and all cortical regions. Surprisingly, in HFD animals FoxO3a was significantly less expressed in the cerebellum and all cortical regions compared to control animals. Even more dramatic, FoxO6 expression dropped about 80% in all brain regions in response to HFD.
  
  
  CONCLUSIONS
  Thus, FoxOs in the CNS showed a highly distinct expression, which in addition was age- and sex-dependent. In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals.
authors.affiliation: Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Zemva
authors.forename: K
authors.initials: K
authors.lastname: Schilbach
authors.forename: O
authors.initials: O
authors.lastname: Stöhr
authors.forename: L
authors.initials: L
authors.lastname: Moll
authors.forename: A
authors.initials: A
authors.lastname: Franko
authors.forename: W
authors.initials: W
authors.lastname: Krone
authors.forename: R J
authors.initials: RJ
authors.lastname: Wiesner
authors.forename: M
authors.initials: M
authors.lastname: Schubert
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C525395:Foxo6 protein, mouse