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
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Roberta Possenti, Giampiero Muccioli, Pamela Petrocchi, Cheryl Cero, Aderville Cabassi, Lucy Vulchanova, Maureen S. Riedl, Monia Manieri, Andrea Frontini, Antonio Giordano, Saverio Cinti, Paolo Govoni, Gallia Graiani, Federico Quaini, Corrado Ghè, Elena Bresciani, Ilaria Bulgarelli, Antonio Torsello, Vittorio Locatelli, Valentina Sanghez, Bjarne D. Larsen, Jorgen S. Petersen, Paola Palanza, Stefano Parmigiani, Anna Moles, Andrea Levi, Alessandro Bartolomucci; Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21. Biochem J 1 January 2012; 441 (1): 511–522. doi: https://doi.org/10.1042/BJ20111165
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