The role of CRF family peptides in the regulation of food intake and anxiety-like behavior

Nakayama, Naoko; Suzuki, Hajime; Li, Jiangbo; Atsuchi, Kaori; Tsai, Minglun; Amitani, Haruka; Asakawa, Akihiro; Inui, Akio

doi:10.1515/bmc.2011.022

Cited by 9 publications

(6 citation statements)

References 79 publications

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“…Consistent with previous literature, a decrease in food intake was also observed following UCN2 dosing (Fig. 2J) (Nakayama et al, 2011;Ohata & Shibasaki, 2004).…”

Section: Acute Ucn2 Treatment Induces Insulin Resistancesupporting

confidence: 92%

Chronic UCN2 Treatment Desensitizes CRHR2 and Improves Insulin Sensitivity

Flaherty

Bézy

et al. 2022

Preprint

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The neuropeptide Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor (GPCR) corticotropin-releasing hormone receptor 2 (CRHR2) expressed in the brain and peripheral metabolic tissues. UCN2 has been reported to improve or worsen insulin sensitivity and glucose uptake in skeletal muscle and have opposing effects on glucose tolerance in vivo. In this report, we examined the acute and chronic effect of UCN2 on glucose metabolism and signaling pathways downstream of CRHR2. Consistent with previous reports, we found that acute dosing of UCN2 induced systemic insulin resistance and hyperglycemia in mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 (UCN2.AAV) resolved metabolic complications, improving glucose tolerance. Phosphoproteomic analysis of acutely treated skeletal muscle revealed dephosphorylation of IRS1 and AKT1S1, which was entirely reversed in UCN2.AAV skeletal muscle. Interestingly, pharmacological studies showed that all human isoforms of CRHR2 recruit Gs, as well as Gi and β-Arrestin, in response to stimulation with UCN2. However, Gi and β-Arrestin recruitment occurs at UCN2 concentrations 10-fold higher than Gs recruitment. Furthermore, pre-treating cells with UCN2 led to internalization of CRHR2 and dampened ligand-dependent increases in cAMP. Consistent with the in vivo results, treatment of mouse soleus muscle with UCN2 ex vivo showed AKT1S1 and IRS1 dephosphorylation and decreased glucose uptake in response to insulin; these responses were blunted when the muscle was pre-incubated with UCN2. These studies demonstrate that exposure to high, chronic concentrations of UCN2 desensitizes CRHR2, thus blocking the effects of acute UCN2, and improving insulin sensitivity, in skeletal muscle and systemically. On the other hand, acute treatment with UCN2 activates CRHR2 through recruitment of Gs which leads to blunted insulin signaling and glucose uptake. These results provide mechanistic insights into how UCN2 regulates insulin sensitivity and glucose metabolism in skeletal muscle and in vivo. Importantly, a working model was derived from these results that unifies the contradictory metabolic effects of UCN2.

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“…Consistent with previous literature, a decrease in food intake was also observed following UCN2 dosing (Fig. 2J) (Nakayama et al, 2011;Ohata & Shibasaki, 2004).…”

Section: Acute Ucn2 Treatment Induces Insulin Resistancesupporting

confidence: 92%

Chronic UCN2 Treatment Desensitizes CRHR2 and Improves Insulin Sensitivity

Flaherty

Bézy

et al. 2022

Preprint

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“…Peripheral administration of VacA increased the number of c-Fos-positive cells in the PVN of the hypothalamus; these cells were also positive for Ucn1, indicating that VacA activated Ucn1-positive neurons in the PVN. Ucn1 is a 40-amino-acid peptide belonging to the CRF peptide family that exerts anorexigenic and anxiogenic effects 34 . Previous studies reported the distribution of Ucn1 in the brain including hypothalamus, Edinger–Westphal nucleus 35 , and the median eminence 36 and the strain dependency in mice 37 .…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice

Suzuki

Ataka

Asakawa

et al. 2019

Sci Rep

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Helicobacter pylori ( Hp ) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.

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“…In contrast, after 2 more hours, NPB caused appetite suppression. The same study evaluated the effects on appetite of co-administration of NPB and corticotropin-releasing factor (CRF), a well-known suppressor of food intake [ 29 ]. Tanaka et al reported that CRF significantly enhanced the suppression of appetite induced by NPB, suggesting an interaction between CRF and urocortin systems [ 11 ].…”

Section: The Role Of Npb In Appetite Modulationmentioning

confidence: 99%

The Role of Neuropeptide B and Its Receptors in Controlling Appetite, Metabolism, and Energy Homeostasis

Wojciechowicz

Billert

Jasaszwili

et al. 2021

IJMS

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Neuropeptide B (NPB) is a peptide hormone that was initially described in 2002. In humans, the biological effects of NPB depend on the activation of two G protein-coupled receptors, NPBWR1 (GPR7) and NPBWR2 (GPR8), and, in rodents, NPBWR1. NPB and its receptors are expressed in the central nervous system (CNS) and in peripheral tissues. NPB is also present in the circulation. In the CNS, NPB modulates appetite, reproduction, pain, anxiety, and emotions. In the peripheral tissues, NPB controls secretion of adrenal hormones, pancreatic beta cells, and various functions of adipose tissue. Experimental downregulation of either NPB or NPBWR1 leads to adiposity. Here, we review the literature with regard to NPB-dependent control of metabolism and energy homeostasis.

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The role of CRF family peptides in the regulation of food intake and anxiety-like behavior

Cited by 9 publications

References 79 publications

Chronic UCN2 Treatment Desensitizes CRHR2 and Improves Insulin Sensitivity

Chronic UCN2 Treatment Desensitizes CRHR2 and Improves Insulin Sensitivity

Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice

The Role of Neuropeptide B and Its Receptors in Controlling Appetite, Metabolism, and Energy Homeostasis

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