Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21 |
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Authors: | Possenti Roberta Muccioli Giampiero Petrocchi Pamela Cero Cheryl Cabassi Aderville Vulchanova Lucy Riedl Maureen S Manieri Monia Frontini Andrea Giordano Antonio Cinti Saverio Govoni Paolo Graiani Gallia Quaini Federico Ghè Corrado Bresciani Elena Bulgarelli Ilaria Torsello Antonio Locatelli Vittorio Sanghez Valentina Larsen Bjarne D Petersen Jorgen S Palanza Paola Parmigiani Stefano Moles Anna Levi Andrea Bartolomucci Alessandro |
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Institution: | Department of Drug Science and Technology, University of Turin, Turin, Italy. |
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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. |
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