Central FoxO3a and FoxO6 Expression is Down­regulated in Obesity Induced Diabetes but not in Aging

J. Zemva; K. Schilbach; O. Stöhr; L. Moll; A. Franko; W. Krone; R. J. Wiesner; M. Schubert

doi:10.1055/s-0031-1297970

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2012; 120(06): 340-350
DOI: 10.1055/s-0031-1297970

Article

Central FoxO3a and FoxO6 Expression is Downregulated in Obesity Induced Diabetes but not in Aging

J. Zemva^*

¹Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany

,

K. Schilbach^*

¹Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany

,

O. Stöhr

¹Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany

,

L. Moll

¹Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany

,

A. Franko

⁴Institute for Vegetative Physiology, University of Cologne, Germany

,

W. Krone

¹Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

³Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany

,

R. J. Wiesner

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

³Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany

⁴Institute for Vegetative Physiology, University of Cologne, Germany

,

M. Schubert

¹Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

³Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany

› Author Affiliations

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.

Conclusion:

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.

Key words

FoxO - aging - mice - diabetes - brain

Full Text

References

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Central FoxO3a and FoxO6 Expression is Down­regulated in Obesity Induced Diabetes but not in Aging

Central FoxO3a and FoxO6 Expression is Downregulated in Obesity Induced Diabetes but not in Aging