The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptormediated mechanism for any VGF peptide. In the present study, we provide a comprehensive in vitro, ex vivo and in vivo identification of a novel pro-lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity for TLQP-21 was higher in the WAT as compared with other tissues, and selectively up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in murine adipocytes via a mechanism encompassing the activation of noradrenaline/β-adrenergic receptors pathways and dose-dependently decreases adipocytes diameters in two models of obesity. In conclusion, we demonstrated a novel and previously uncharacterized peripheral lipolytic pathway encompassing the VGF peptide TLQP-21. Targeting the sympathetic nerve-adipocytes interaction might prove to be a novel approach for the treatment of obesityassociated metabolic complications. © The Authors Journal compilation © 2012 Biochemical Society.
Possenti, R., Muccioli, G., Petrocchi, P., Cero, C., Cabassi, A., Vulchanova, L., et al. (2012). Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21. BIOCHEMICAL JOURNAL, 441(1), 511-522 [10.1042/BJ20111165].
|Citazione:||Possenti, R., Muccioli, G., Petrocchi, P., Cero, C., Cabassi, A., Vulchanova, L., et al. (2012). Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21. BIOCHEMICAL JOURNAL, 441(1), 511-522 [10.1042/BJ20111165].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21|
|Autori:||Possenti, R; Muccioli, G; Petrocchi, P; Cero, C; Cabassi, A; Vulchanova, L; Riedl, MS; Manieri, M; Frontini, A; Giordano, A; Cinti, S; Govoni, P; Graiani, G; Quaini, F; Ghè, C; Bresciani, E; Bulgarelli, I; Torsello, A; Locatelli, V; Sanghez, V; Larsen, BD; Petersen, JS; Palanza, P; Parmigiani, S; Moles, A; Levi, A; Bartolomucci, A.|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1042/BJ20111165|
|Appare nelle tipologie:||01 - Articolo su rivista|