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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

Representative darkfield photomicrographs showing Ucn 3 mRNA expression (white clusters) in a wildtype mouse (A), an ob/ob obese mouse (B), and an ob/ob mouse treated with leptin (0.1 mg/kg/day for 2 days) (C). (D) Summary of Ucn 3 mRNA levels in the MeA of WT and Ob/ob obese mice treated with vehicle or leptin. The Ucn 3 mRNA levels in an additional group of Ob/ob mice that was paired-fed were also determined. Different letters represent statistical significance: p < 0.05. MeApd, medial nucleus of amygdala, posterodorsal part; opt, optic tract. Scale bar = 20 μm.
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Figure 1: Representative darkfield photomicrographs showing Ucn 3 mRNA expression (white clusters) in a wildtype mouse (A), an ob/ob obese mouse (B), and an ob/ob mouse treated with leptin (0.1 mg/kg/day for 2 days) (C). (D) Summary of Ucn 3 mRNA levels in the MeA of WT and Ob/ob obese mice treated with vehicle or leptin. The Ucn 3 mRNA levels in an additional group of Ob/ob mice that was paired-fed were also determined. Different letters represent statistical significance: p < 0.05. MeApd, medial nucleus of amygdala, posterodorsal part; opt, optic tract. Scale bar = 20 μm.

Mentions: The expression of Ucn 3 has also been examined in genetically obese rodent models. Food deprivation increases Ucn 3 mRNA expression in the dorsal part of the medial amygdala (MeD) in obese Fa/Fa Zuker rats and has no effect on Ucn 3 expression in the rPFH (Poulin et al., 2012). In contrast, lean Fa/? rats show increased Ucn 3 expression in the rPFH but not the MeD after food deprivation (Poulin et al., 2012). Ucn 3 mRNA expression returns to normal after 24 h of refeeding (Poulin et al., 2012). In ob/ob obese mice, Ucn 3 expression is significantly reduced in the MeA (Figure 1; Li and Vale, 2002), and leptin treatment reverses Ucn 3 expression in this area. Interestingly, pair-feeding in ob/ob mice failed to modulate Ucn 3 expression in the MeA. These results indicate that Ucn 3 expression in the MeA is regulated by leptin. Taken together, these studies further support the notion that endogenous Ucn 3 in the brain is sensitive to metabolic signals and energy status and potentially plays an important role in regulating energy homeostasis.


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)

Representative darkfield photomicrographs showing Ucn 3 mRNA expression (white clusters) in a wildtype mouse (A), an ob/ob obese mouse (B), and an ob/ob mouse treated with leptin (0.1 mg/kg/day for 2 days) (C). (D) Summary of Ucn 3 mRNA levels in the MeA of WT and Ob/ob obese mice treated with vehicle or leptin. The Ucn 3 mRNA levels in an additional group of Ob/ob mice that was paired-fed were also determined. Different letters represent statistical significance: p < 0.05. MeApd, medial nucleus of amygdala, posterodorsal part; opt, optic tract. Scale bar = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Representative darkfield photomicrographs showing Ucn 3 mRNA expression (white clusters) in a wildtype mouse (A), an ob/ob obese mouse (B), and an ob/ob mouse treated with leptin (0.1 mg/kg/day for 2 days) (C). (D) Summary of Ucn 3 mRNA levels in the MeA of WT and Ob/ob obese mice treated with vehicle or leptin. The Ucn 3 mRNA levels in an additional group of Ob/ob mice that was paired-fed were also determined. Different letters represent statistical significance: p < 0.05. MeApd, medial nucleus of amygdala, posterodorsal part; opt, optic tract. Scale bar = 20 μm.
Mentions: The expression of Ucn 3 has also been examined in genetically obese rodent models. Food deprivation increases Ucn 3 mRNA expression in the dorsal part of the medial amygdala (MeD) in obese Fa/Fa Zuker rats and has no effect on Ucn 3 expression in the rPFH (Poulin et al., 2012). In contrast, lean Fa/? rats show increased Ucn 3 expression in the rPFH but not the MeD after food deprivation (Poulin et al., 2012). Ucn 3 mRNA expression returns to normal after 24 h of refeeding (Poulin et al., 2012). In ob/ob obese mice, Ucn 3 expression is significantly reduced in the MeA (Figure 1; Li and Vale, 2002), and leptin treatment reverses Ucn 3 expression in this area. Interestingly, pair-feeding in ob/ob mice failed to modulate Ucn 3 expression in the MeA. These results indicate that Ucn 3 expression in the MeA is regulated by leptin. Taken together, these studies further support the notion that endogenous Ucn 3 in the brain is sensitive to metabolic signals and energy status and potentially plays an important role in regulating energy homeostasis.

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