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Central urocortin 3 and type 2 corticotropin-releasing factor receptor in the regulation of energy homeostasis: critical involvement of the ventromedial hypothalamus.

Chen P, Hover CV, Lindberg D, Li C - Front Endocrinol (Lausanne) (2013)

Bottom Line: The effects of CRF are mediated by two G-protein-coupled receptors, type 1 and type 2 CRF receptors (CRF(1) and CRF(2)).Ucn 3 is the latest addition of the CRF family of peptides and is highly selective for CRF(2).The brain loci that mediate the central effects of Ucn 3 remain to be fully determined.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Virginia Health System Charlottesville, VA, USA.

ABSTRACT
The vital role of the corticotropin-releasing factor (CRF) peptide family in the brain in coordinating response to stress has been extensively documented. The effects of CRF are mediated by two G-protein-coupled receptors, type 1 and type 2 CRF receptors (CRF(1) and CRF(2)). While the functional role of CRF(1) in hormonal and behavioral adaptation to stress is well-known, the physiological significance of CRF(2) remains to be fully appreciated. Accumulating evidence has indicated that CRF(2) and its selective ligands including urocortin 3 (Ucn 3) are important molecular mediators in regulating energy balance. Ucn 3 is the latest addition of the CRF family of peptides and is highly selective for CRF(2). Recent studies have shown that central Ucn 3 is important in a number of homeostatic functions including suppression of feeding, regulation of blood glucose levels, and thermoregulation, thus reinforcing the functional role of central CRF(2) in metabolic regulation. The brain loci that mediate the central effects of Ucn 3 remain to be fully determined. Anatomical and functional evidence has suggested that the ventromedial hypothalamus (VMH), where CRF(2) is prominently expressed, appears to be instrumental in mediating the effects of Ucn 3 on energy balance, permitting Ucn 3-mediated modulation of feeding and glycemic control. Thus, the Ucn 3-VMH CRF(2) system is an important neural pathway in the regulation of energy homeostasis and potentially plays a critical role in energy adaptation in response to metabolic perturbations and stress to maintain energy balance.

No MeSH data available.


Related in: MedlinePlus

(A) Darkfield photomicrograph showing the injection site (green circle) of an adenoviral vector encoding Cre-regulated expression of farnesylated green fluorescent protein (GFPf) delivered into the VMH of a CRFR2-Cre mouse. The expression of GFPf is normally silenced due to a Cre-regulated transcription block sequence inserted upstream of GFPf reporter cassette. In the presence of Cre, the transcription block sequence is removed to allow GFPf to be expressed in Cre-positive cells. (B) Darkfield photomicrograph depicting the distribution of VMH CRFR2-positive fibers (golden staining) within the rostral ventrolateral medulla (RVLM). ARH, arcuate nucleus of hypothalamus; MARN, magnocellular reticular nucleus; ME, median eminence; Py, pyramidal tract; Tu, tuberal nucleus; V3, third ventricle; VII, facial nucleus; VMHdn, dorsomedial part of the ventromedial nucleus of hypothalamus. Scale bar = 50 μm.
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Figure 3: (A) Darkfield photomicrograph showing the injection site (green circle) of an adenoviral vector encoding Cre-regulated expression of farnesylated green fluorescent protein (GFPf) delivered into the VMH of a CRFR2-Cre mouse. The expression of GFPf is normally silenced due to a Cre-regulated transcription block sequence inserted upstream of GFPf reporter cassette. In the presence of Cre, the transcription block sequence is removed to allow GFPf to be expressed in Cre-positive cells. (B) Darkfield photomicrograph depicting the distribution of VMH CRFR2-positive fibers (golden staining) within the rostral ventrolateral medulla (RVLM). ARH, arcuate nucleus of hypothalamus; MARN, magnocellular reticular nucleus; ME, median eminence; Py, pyramidal tract; Tu, tuberal nucleus; V3, third ventricle; VII, facial nucleus; VMHdn, dorsomedial part of the ventromedial nucleus of hypothalamus. Scale bar = 50 μm.

Mentions: Recently, using a conditional viral tracing approach, we have found that VMH neurons project to a number of important brainstem autonomic centers including the parabrachial nucleus, C1 catecholaminergic cell group in the rostral ventrolateral medulla, and the nucleus of solitary tract (Lindberg et al., 2011). Moreover, we have used the same approach to find that CRF2-positive cells in the VMH show similar axonal projections to these brainstem areas (Figure 3; Lindberg et al., 2011). These studies demonstrate that VMH neurons, including cells that express CRF2, can potentially modulate SNS activity by direct projections to brainstem autonomic centers.


Central urocortin 3 and type 2 corticotropin-releasing factor receptor in the regulation of energy homeostasis: critical involvement of the ventromedial hypothalamus.

Chen P, Hover CV, Lindberg D, Li C - Front Endocrinol (Lausanne) (2013)

(A) Darkfield photomicrograph showing the injection site (green circle) of an adenoviral vector encoding Cre-regulated expression of farnesylated green fluorescent protein (GFPf) delivered into the VMH of a CRFR2-Cre mouse. The expression of GFPf is normally silenced due to a Cre-regulated transcription block sequence inserted upstream of GFPf reporter cassette. In the presence of Cre, the transcription block sequence is removed to allow GFPf to be expressed in Cre-positive cells. (B) Darkfield photomicrograph depicting the distribution of VMH CRFR2-positive fibers (golden staining) within the rostral ventrolateral medulla (RVLM). ARH, arcuate nucleus of hypothalamus; MARN, magnocellular reticular nucleus; ME, median eminence; Py, pyramidal tract; Tu, tuberal nucleus; V3, third ventricle; VII, facial nucleus; VMHdn, dorsomedial part of the ventromedial nucleus of hypothalamus. Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539675&req=5

Figure 3: (A) Darkfield photomicrograph showing the injection site (green circle) of an adenoviral vector encoding Cre-regulated expression of farnesylated green fluorescent protein (GFPf) delivered into the VMH of a CRFR2-Cre mouse. The expression of GFPf is normally silenced due to a Cre-regulated transcription block sequence inserted upstream of GFPf reporter cassette. In the presence of Cre, the transcription block sequence is removed to allow GFPf to be expressed in Cre-positive cells. (B) Darkfield photomicrograph depicting the distribution of VMH CRFR2-positive fibers (golden staining) within the rostral ventrolateral medulla (RVLM). ARH, arcuate nucleus of hypothalamus; MARN, magnocellular reticular nucleus; ME, median eminence; Py, pyramidal tract; Tu, tuberal nucleus; V3, third ventricle; VII, facial nucleus; VMHdn, dorsomedial part of the ventromedial nucleus of hypothalamus. Scale bar = 50 μm.
Mentions: Recently, using a conditional viral tracing approach, we have found that VMH neurons project to a number of important brainstem autonomic centers including the parabrachial nucleus, C1 catecholaminergic cell group in the rostral ventrolateral medulla, and the nucleus of solitary tract (Lindberg et al., 2011). Moreover, we have used the same approach to find that CRF2-positive cells in the VMH show similar axonal projections to these brainstem areas (Figure 3; Lindberg et al., 2011). These studies demonstrate that VMH neurons, including cells that express CRF2, can potentially modulate SNS activity by direct projections to brainstem autonomic centers.

Bottom Line: The effects of CRF are mediated by two G-protein-coupled receptors, type 1 and type 2 CRF receptors (CRF(1) and CRF(2)).Ucn 3 is the latest addition of the CRF family of peptides and is highly selective for CRF(2).The brain loci that mediate the central effects of Ucn 3 remain to be fully determined.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Virginia Health System Charlottesville, VA, USA.

ABSTRACT
The vital role of the corticotropin-releasing factor (CRF) peptide family in the brain in coordinating response to stress has been extensively documented. The effects of CRF are mediated by two G-protein-coupled receptors, type 1 and type 2 CRF receptors (CRF(1) and CRF(2)). While the functional role of CRF(1) in hormonal and behavioral adaptation to stress is well-known, the physiological significance of CRF(2) remains to be fully appreciated. Accumulating evidence has indicated that CRF(2) and its selective ligands including urocortin 3 (Ucn 3) are important molecular mediators in regulating energy balance. Ucn 3 is the latest addition of the CRF family of peptides and is highly selective for CRF(2). Recent studies have shown that central Ucn 3 is important in a number of homeostatic functions including suppression of feeding, regulation of blood glucose levels, and thermoregulation, thus reinforcing the functional role of central CRF(2) in metabolic regulation. The brain loci that mediate the central effects of Ucn 3 remain to be fully determined. Anatomical and functional evidence has suggested that the ventromedial hypothalamus (VMH), where CRF(2) is prominently expressed, appears to be instrumental in mediating the effects of Ucn 3 on energy balance, permitting Ucn 3-mediated modulation of feeding and glycemic control. Thus, the Ucn 3-VMH CRF(2) system is an important neural pathway in the regulation of energy homeostasis and potentially plays a critical role in energy adaptation in response to metabolic perturbations and stress to maintain energy balance.

No MeSH data available.


Related in: MedlinePlus