Limits...
Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

Kajimura D, Paone R, Mann JJ, Karsenty G - Mol Metab (2014)

Bottom Line: Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla.Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla.FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

ABSTRACT
The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1 Dbh-/- mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.

No MeSH data available.


Related in: MedlinePlus

(A) Putative FoxO1 binding sites in the Dbh promoter in human, mouse, rat, horse, dog, chicken and zebrafish. (B) Binding of FoxO1 to the Dbh promoter detected by Chromatin immuno-precipitation (ChIP) assay. (C) DNA cotransfections assays in HEK cells using a FoxO1 expression vector and reporter vectors containing fragments of Dbh promoter fused to the Luciferase gene. (D) Dbh expression in FoxO1fl/fl and FoxO1Dbh−/− brainstem. (E) In situ hybridization analysis of the Dbh expression in the locus coeruleus, adrenal gland, the dorsal root ganglion, and superior cervical ganglion.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4209360&req=5

fig2: (A) Putative FoxO1 binding sites in the Dbh promoter in human, mouse, rat, horse, dog, chicken and zebrafish. (B) Binding of FoxO1 to the Dbh promoter detected by Chromatin immuno-precipitation (ChIP) assay. (C) DNA cotransfections assays in HEK cells using a FoxO1 expression vector and reporter vectors containing fragments of Dbh promoter fused to the Luciferase gene. (D) Dbh expression in FoxO1fl/fl and FoxO1Dbh−/− brainstem. (E) In situ hybridization analysis of the Dbh expression in the locus coeruleus, adrenal gland, the dorsal root ganglion, and superior cervical ganglion.

Mentions: FoxO1Dbh−/− mice were generated by crossing FoxO1fl/+ mice with FoxO1fl/+; Dbh-cre mice as previously described in Refs. [11–13]. For all the analyses, C57BL/6J background, 9 month-old male mice were used except for deletion specificity, which was done in 9 month-old male and female FoxO1Dbh−/− mice (Figure 1C and Supplemental Figure 1B), and FoxO1 and Dbh expression, which was done in 6 week-old and P10 male mice for locus coeruleus, and 6 week-old male mice for adrenal gland, the dorsal root ganglion, superior cervical ganglion, and ileum (Figures 1A, D, and 2E and Supplemental Figures 1A and 2). All procedures involving animals were approved by CUMC IACUC and conform to the relevant regulatory standards.


Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

Kajimura D, Paone R, Mann JJ, Karsenty G - Mol Metab (2014)

(A) Putative FoxO1 binding sites in the Dbh promoter in human, mouse, rat, horse, dog, chicken and zebrafish. (B) Binding of FoxO1 to the Dbh promoter detected by Chromatin immuno-precipitation (ChIP) assay. (C) DNA cotransfections assays in HEK cells using a FoxO1 expression vector and reporter vectors containing fragments of Dbh promoter fused to the Luciferase gene. (D) Dbh expression in FoxO1fl/fl and FoxO1Dbh−/− brainstem. (E) In situ hybridization analysis of the Dbh expression in the locus coeruleus, adrenal gland, the dorsal root ganglion, and superior cervical ganglion.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4209360&req=5

fig2: (A) Putative FoxO1 binding sites in the Dbh promoter in human, mouse, rat, horse, dog, chicken and zebrafish. (B) Binding of FoxO1 to the Dbh promoter detected by Chromatin immuno-precipitation (ChIP) assay. (C) DNA cotransfections assays in HEK cells using a FoxO1 expression vector and reporter vectors containing fragments of Dbh promoter fused to the Luciferase gene. (D) Dbh expression in FoxO1fl/fl and FoxO1Dbh−/− brainstem. (E) In situ hybridization analysis of the Dbh expression in the locus coeruleus, adrenal gland, the dorsal root ganglion, and superior cervical ganglion.
Mentions: FoxO1Dbh−/− mice were generated by crossing FoxO1fl/+ mice with FoxO1fl/+; Dbh-cre mice as previously described in Refs. [11–13]. For all the analyses, C57BL/6J background, 9 month-old male mice were used except for deletion specificity, which was done in 9 month-old male and female FoxO1Dbh−/− mice (Figure 1C and Supplemental Figure 1B), and FoxO1 and Dbh expression, which was done in 6 week-old and P10 male mice for locus coeruleus, and 6 week-old male mice for adrenal gland, the dorsal root ganglion, superior cervical ganglion, and ileum (Figures 1A, D, and 2E and Supplemental Figures 1A and 2). All procedures involving animals were approved by CUMC IACUC and conform to the relevant regulatory standards.

Bottom Line: Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla.Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla.FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

ABSTRACT
The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1 Dbh-/- mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.

No MeSH data available.


Related in: MedlinePlus