Anorexigenic effects induced by RVD-hemopressin(α) administration

Claudio Ferrante, Lucia Recinella, Sheila Leone, Annalisa Chiavaroli, Chiara Di Nisio, Sara Martinotti, Adriano Mollica, Giorgia Macedonio, Azzurra Stefanucci, Szabolcs Dvorácskó, C. Tömböly, Luciano De Petrocellis, Michele Vacca, Luigi Brunetti, Giustino Orlando

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background Hemopressin, VD-hemopressin(α) and RVD-hemopressin(α) are hemoglobin α chain derived-peptides which have been found in mouse brain, and where they modulate cannabinoid (CB) receptor function. The nonapeptide hemopressin has been reported to inhibit feeding after both central and peripheral administration, possibly playing a role of antagonist/inverse agonist of CB1 receptors, and consequently blocking the orexigenic effects of endogenous cannabinoids. VD-hemopressin(α) and RVD- hemopressin(α), are N-terminal extended forms of hemopressin. VD-hemopressin(α) has CB1 agonist activity, and as such it has been shown to stimulate feeding. RVD-hemopressin(α) is reported to play a negative allosteric modulatory function on CB1 receptors, but there are no data on its possible effects on feeding and metabolic control. Methods We have studied, in rats, the effects of 14 daily intraperitoneal (ip) injections of RVD-hemopressin(α) (10 nmol). Results We found that RVD-hemopressin(α) treatment inhibited food intake while total body weight was not affected. The null effect on body weight despite diminished feeding could be related to decreased uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue (BAT). We also investigated the underlying neuromodulatory effects of RVD-hemopressin(α) and found it to down regulate proopiomelanocortin (POMC) gene expression, together with norepinephrine (NE) levels, in the hypothalamus. Conclusions In conclusion, RVD-hemopressin(α) administration has an anorectic effect, possibly related to inhibition of POMC and NE levels in the hypothalamus. Despite decreased food intake, body weight is not affected by RVD-hemopressin(α) treatment, possibly due to inhibition of UCP-1 gene expression in BAT.

Original languageEnglish
Pages (from-to)1402-1407
Number of pages6
JournalPharmacological Reports
Volume69
Issue number6
DOIs
Publication statusPublished - Dec 1 2017

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Cannabinoid Receptor CB1
Pro-Opiomelanocortin
Brown Adipose Tissue
Body Weight
hemopressin
Gene Expression
Hypothalamus
Norepinephrine
Eating
Appetite Depressants
Cannabinoid Receptors
Cannabinoids
Intraperitoneal Injections
Hemoglobins
Down-Regulation
Peptides
Brain
Therapeutics
Uncoupling Protein 1

Keywords

  • Feeding
  • Norepinephrine
  • Proopiomelanocortin
  • RVD-hemopressin(α)
  • Uncoupling protein-1

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ferrante, C., Recinella, L., Leone, S., Chiavaroli, A., Di Nisio, C., Martinotti, S., ... Orlando, G. (2017). Anorexigenic effects induced by RVD-hemopressin(α) administration. Pharmacological Reports, 69(6), 1402-1407. https://doi.org/10.1016/j.pharep.2017.05.015

Anorexigenic effects induced by RVD-hemopressin(α) administration. / Ferrante, Claudio; Recinella, Lucia; Leone, Sheila; Chiavaroli, Annalisa; Di Nisio, Chiara; Martinotti, Sara; Mollica, Adriano; Macedonio, Giorgia; Stefanucci, Azzurra; Dvorácskó, Szabolcs; Tömböly, C.; De Petrocellis, Luciano; Vacca, Michele; Brunetti, Luigi; Orlando, Giustino.

In: Pharmacological Reports, Vol. 69, No. 6, 01.12.2017, p. 1402-1407.

Research output: Contribution to journalArticle

Ferrante, C, Recinella, L, Leone, S, Chiavaroli, A, Di Nisio, C, Martinotti, S, Mollica, A, Macedonio, G, Stefanucci, A, Dvorácskó, S, Tömböly, C, De Petrocellis, L, Vacca, M, Brunetti, L & Orlando, G 2017, 'Anorexigenic effects induced by RVD-hemopressin(α) administration', Pharmacological Reports, vol. 69, no. 6, pp. 1402-1407. https://doi.org/10.1016/j.pharep.2017.05.015
Ferrante C, Recinella L, Leone S, Chiavaroli A, Di Nisio C, Martinotti S et al. Anorexigenic effects induced by RVD-hemopressin(α) administration. Pharmacological Reports. 2017 Dec 1;69(6):1402-1407. https://doi.org/10.1016/j.pharep.2017.05.015
Ferrante, Claudio ; Recinella, Lucia ; Leone, Sheila ; Chiavaroli, Annalisa ; Di Nisio, Chiara ; Martinotti, Sara ; Mollica, Adriano ; Macedonio, Giorgia ; Stefanucci, Azzurra ; Dvorácskó, Szabolcs ; Tömböly, C. ; De Petrocellis, Luciano ; Vacca, Michele ; Brunetti, Luigi ; Orlando, Giustino. / Anorexigenic effects induced by RVD-hemopressin(α) administration. In: Pharmacological Reports. 2017 ; Vol. 69, No. 6. pp. 1402-1407.
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AU - Ferrante, Claudio

AU - Recinella, Lucia

AU - Leone, Sheila

AU - Chiavaroli, Annalisa

AU - Di Nisio, Chiara

AU - Martinotti, Sara

AU - Mollica, Adriano

AU - Macedonio, Giorgia

AU - Stefanucci, Azzurra

AU - Dvorácskó, Szabolcs

AU - Tömböly, C.

AU - De Petrocellis, Luciano

AU - Vacca, Michele

AU - Brunetti, Luigi

AU - Orlando, Giustino

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N2 - Background Hemopressin, VD-hemopressin(α) and RVD-hemopressin(α) are hemoglobin α chain derived-peptides which have been found in mouse brain, and where they modulate cannabinoid (CB) receptor function. The nonapeptide hemopressin has been reported to inhibit feeding after both central and peripheral administration, possibly playing a role of antagonist/inverse agonist of CB1 receptors, and consequently blocking the orexigenic effects of endogenous cannabinoids. VD-hemopressin(α) and RVD- hemopressin(α), are N-terminal extended forms of hemopressin. VD-hemopressin(α) has CB1 agonist activity, and as such it has been shown to stimulate feeding. RVD-hemopressin(α) is reported to play a negative allosteric modulatory function on CB1 receptors, but there are no data on its possible effects on feeding and metabolic control. Methods We have studied, in rats, the effects of 14 daily intraperitoneal (ip) injections of RVD-hemopressin(α) (10 nmol). Results We found that RVD-hemopressin(α) treatment inhibited food intake while total body weight was not affected. The null effect on body weight despite diminished feeding could be related to decreased uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue (BAT). We also investigated the underlying neuromodulatory effects of RVD-hemopressin(α) and found it to down regulate proopiomelanocortin (POMC) gene expression, together with norepinephrine (NE) levels, in the hypothalamus. Conclusions In conclusion, RVD-hemopressin(α) administration has an anorectic effect, possibly related to inhibition of POMC and NE levels in the hypothalamus. Despite decreased food intake, body weight is not affected by RVD-hemopressin(α) treatment, possibly due to inhibition of UCP-1 gene expression in BAT.

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