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 receptor-mediated 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 obesity-associated metabolic complications.

Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21 / R., Possenti; G., Muccioli; P., Petrocchi; C., Cero; Cabassi, Aderville; L., Vulchanova; M. S., Riedl; M., Manieri; A., Frontini; A., Giordano; S., Cinti; Govoni, Paolo; Graiani, Gallia; Quaini, Federico; C., Ghe; E., Bresciani; I., Bulgarelli; A., Torsello; V., Locatelli; Sanghez, Valentina; B. D., Larsen; J. S., Petersen; Palanza, Paola; Parmigiani, Stefano; A., Moles; A., Levi; Bartolomucci, Alessandro. - In: BIOCHEMICAL JOURNAL. - ISSN 0264-6021. - 441:(2012), pp. 511-522. [10.1042/BJ20111165]

Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21

CABASSI, Aderville;GOVONI, Paolo;GRAIANI, Gallia;QUAINI, Federico;SANGHEZ, Valentina;PALANZA, Paola;PARMIGIANI, Stefano;BARTOLOMUCCI, Alessandro
2012-01-01

Abstract

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 receptor-mediated 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 obesity-associated metabolic complications.
Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21 / R., Possenti; G., Muccioli; P., Petrocchi; C., Cero; Cabassi, Aderville; L., Vulchanova; M. S., Riedl; M., Manieri; A., Frontini; A., Giordano; S., Cinti; Govoni, Paolo; Graiani, Gallia; Quaini, Federico; C., Ghe; E., Bresciani; I., Bulgarelli; A., Torsello; V., Locatelli; Sanghez, Valentina; B. D., Larsen; J. S., Petersen; Palanza, Paola; Parmigiani, Stefano; A., Moles; A., Levi; Bartolomucci, Alessandro. - In: BIOCHEMICAL JOURNAL. - ISSN 0264-6021. - 441:(2012), pp. 511-522. [10.1042/BJ20111165]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2383004
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